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Abstract Background The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. Methods The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/BS9GM . A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. Results The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). Conclusion IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis.

Background: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis. Methods: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF):https://doi.org/10.17605/OSF.IO/BS9GM. A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group. Results: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*). Conclusion: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis. [ABSTRACT FROM AUTHOR]

Introduction: Filipino Americans (FAs) are at high risk for developing type 2 diabetes despite other Asian phenotypes. Evidence suggests that pro-inflammatory interleukin-18 (IL-18) and anti-inflammatory adiponectin biomarkers associated with visceral adipose tissue (VAT) may explain this risk. Objectives: This study aimed to quantify the biomarkers in relation to standard ranges of VAT or typical circulating concentration ranges reported in the literature of IL-18 and adiponectin, examine relationships of these markers, and determine if they were different among those participants without diabetes, prediabetes, and diabetes. Methods: A cross-sectional study was used to enroll FAs without diabetes, prediabetes, or diabetes. VAT was measured using the InBody 570© Body Composition Analyzer. Blood samples were obtained to assess plasma concentrations of IL-18 and adiponectin using enzyme-linked immunosorbent assay. All analyses were conducted using a 5% type I error rate. Mean ±SD and percentages were used to describe the sample and data where appropriate. Pearson's correlations (R) were calculated to determine the relationships between VAT and IL-18 in each group. Analysis of variance was used to determine differences in VAT, IL-18, and adiponectin among groups. Further, nonparametric procedures examined the differences in adiponectin among those within groups. Results: Seventy-five participants were enrolled. Biomarkers above the typical concentration range were observed for VAT, IL-18, and adiponectin. Adiponectin significantly differed among groups with lower values in the diabetes group vs. the nondiabetes group. Conclusions: The findings indicate that while inflammation-related biomarkers, such as adiponectin, correlate with VAT and may serve as indicators of increased risk of type 2 diabetes in FAs, correlation alone does not establish causality. [ABSTRACT FROM AUTHOR]

Background: Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a protein which in humans is encoded by the IL18 gene, it is a member of the IL 1 family and has a molecular weight of 18 kDa. Innate and adaptive immunity can be regulated by IL-18, and disorders involving its dysregulation might result in inflammatory or autoimmune conditions. Aim of the Work: To distinguish between acute kidney injury (AKI) and chronic renal failure (CRF), this research investigates the utility of IL-18 as a novel biomarker and examines how age affects its level. Materials and Methods: Three hundred participants were included and divided into three groups using the following methodology. Group I consisted of 100 control subjects who were split up by age and gender. Group II consisted of 100 AKI patients who were divided into two groups and subgroups based on age and gender. Group III, which consisted of 100 CRF (hemodialyzed patients), was divided into two groups and subgroups, as patients with acute renal injury and previously healthy people. Patients’ blood was drawn to conduct a laboratory investigation blood urea, serum creatinine, sodium, potassium, pH, GFR and PCO2. Results: Patients with CRF had higher serum levels of IL-18 than patients with AKI, regardless of gender, and both groups of patients had levels of IL-18 that rise with age. Conclusion: IL-18 is a reliable indicator for the differentiation between AKI and CRF patients receiving hemodialysis and its level correlates with age independent with gender.

Background: Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a protein which in humans is encoded by the IL18 gene, it is a member of the IL 1 family and has a molecular weight of 18 kDa. Innate and adaptive immunity can be regulated by IL-18, and disorders involving its dysregulation might result in inflammatory or autoimmune conditions. Aim of the Work: To distinguish between acute kidney injury (AKI) and chronic renal failure (CRF), this research investigates the utility of IL-18 as a novel biomarker and examines how age affects its level. Materials and Methods: Three hundred participants were included and divided into three groups using the following methodology. Group I consisted of 100 control subjects who were split up by age and gender. Group II consisted of 100 AKI patients who were divided into two groups and subgroups based on age and gender. Group III, which consisted of 100 CRF (hemodialyzed patients), was divided into two groups and subgroups, as patients with acute renal injury and previously healthy people. Patients' blood was drawn to conduct a laboratory investigation blood urea, serum creatinine, sodium, potassium, pH, GFR and PCO2. Results: Patients with CRF had higher serum levels of IL-18 than patients with AKI, regardless of gender, and both groups of patients had levels of IL-18 that rise with age. Conclusion: IL-18 is a reliable indicator for the differentiation between AKI and CRF patients receiving hemodialysis and its level correlates with age independent with gender. [ABSTRACT FROM AUTHOR]

Chenhao Xing,1 Yamin Lu,2 Guangxia Liu,2 Fang Chen,2 Zhan Hou,2 Yiwen Zhang2 1Graduate School of Hebei North University, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 2Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Yamin Lu, Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China, Tel +86 15833956939, Email xyluyamin@163.comObjective: The purpose of the study was to investigate the expression levels and correlation of inflammatory factors such as miR-377-3p and TGF-β in patients with diabetic kidney disease (DKD), and to investigate the regulatory mechanism of transfection of miR-377-3p on the inflammatory response of HK-2 cell induced by high glucose.Methods: According to UACR, patients were divided into normal albuminuria group (Con, n = 29), microalbuminuria group (Micro, n = 31) and macroalbuminuria group (Macro, n = 30), analyzed the correlation and influencing factors between DKD and inflammatory factor. HK-2 cells were randomly divided into four groups: normal control group (NC), high glucose group (HG), miR-377-3p overexpression group (MIN), and miR-377-3p inhibition group (IN). After transfection of miR-377-3p mimics and inhibitors, the contents of TGF-β, IL-6 and IL-18 were detected by RT-PCR and Western blot.Results: The levels of miR-377-3p, TGF-β, IL-6 and IL-18 in both Micro group and Macro group were significantly higher than those in Con group (P < 0.05); Pearson correlation analysis showed that miR-377-3p was positively correlated with UACR, TG, TGF-β, IL-6 and IL-18, and negatively correlated with GFR (P < 0.05). Cell experiment: RT-PCR and Western blot results showed that miR-377-3p, TGF-β, IL-6 and IL-18 in HG group were significantly higher than those in NC group (P < 0.05). After transfection with miR-377-3p inhibitor, the levels of miR-377-3p, TGF-β, IL-6 and IL-18 in IN group were significantly decreased compared with HG group and MIN group.Conclusion: miR-377-3p expression was elevated both in serum of DKD patients and in HK-2 cells with high glucose induced injury, overexpression of miR-377-3p exacerbates the damage to HK-2 cells and promotes the progression of DKD. Silencing miR-377-3p can potentially regulate the levels of inflammatory factors in HK-2 cells by targeting downregulation of TGF-β expression, thereby mitigating the damage to HK-2 cells and delaying the development of diabetic kidney disease.Keywords: miR-377-3p, transforming growth factor beta, interleukin 6, interleukin 18, renal tubular epithelial cells

Background: Aberrant deoxyribonucleic acid (DNA) contributes to inflammasome orchestrated progression of chronic inflammatory diseases like diabetes and periodontitis. The purpose of the present study was to estimate salivary levels of DNA sensing inflammasomes, absent in melanoma 2 (AIM2), interferon γ inducible protein (IFI16), and cytokine interleukin 18 (IL18) in individuals with periodontitis, diabetes, and healthy controls and interpret its association with periodontal and diabetic parameters. Methods: Salivary levels of AIM2, IFI16, and IL18 were estimated by enzyme linked immunosorbent assay (ELISA) in a total of 120 individuals (n = 30 in each group), namely, healthy (Group 1), periodontitis (Group 2), diabetes (Group 3), and diabetes with periodontitis (Group 4). Correlations of inflammasome levels and periodontal clinical parameters—plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), clinical attachment level (CAL), and periodontal inflamed surface area (PISA) were performed. Multiple regression was carried out to predict AIM2 and IFI16 with various independent variables. Results: The mean salivary levels of AIM2, IFI16, and IL18 were highest in diabetes with periodontitis (Group 4) and least in healthy (Group 1) and statistically significant between the groups (p = 0.000). Significant positive correlation between clinical periodontal parameters and AIM2, IFI16, and IL18 was present (p ≤ 0.05). Multiple regression showed glycated hemoglobin (HbA1C) (p = 0.002), GI (p = 0.016), PISA (p = 0.002), and CAL (p = 0.004) were significant predictors of AIM2, while HbA1C (p = 0.012), PISA (p = 0.003), and CAL (p = 0.007) predicted IFI16. Conclusion: The results of the present study showed higher levels of AIM2, IFI16, and IL18 in saliva of individuals with diabetes and periodontitis. HbA1C, PISA, and CAL were significant independent predictors of salivary AIM2 and IFI16 levels. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the expression levels and correlation of inflammatory factors such as miR-377-3p and TGF-β in patients with diabetic kidney disease (DKD), and to investigate the regulatory mechanism of transfection of miR-377-3p on the inflammatory response of HK-2 cell induced by high glucose. Methods: According to UACR, patients were divided into normal albuminuria group (Con, n = 29), microalbuminuria group (Micro, n = 31) and macroalbuminuria group (Macro, n = 30), analyzed the correlation and influencing factors between DKD and inflammatory factor. HK-2 cells were randomly divided into four groups: normal control group (NC), high glucose group (HG), miR-377-3p overexpression group (MIN), and miR-377-3p inhibition group (IN). After transfection of miR-377-3p mimics and inhibitors, the contents of TGF-β, IL-6 and IL-18 were detected by RT-PCR and Western blot. Results: The levels of miR-377-3p, TGF-β, IL-6 and IL-18 in both Micro group and Macro group were significantly higher than those in Con group (P < 0.05); Pearson correlation analysis showed that miR-377-3p was positively correlated with UACR, TG, TGF-β, IL-6 and IL-18, and negatively correlated with GFR (P < 0.05). Cell experiment: RT-PCR and Western blot results showed that miR-377-3p, TGF-β, IL-6 and IL-18 in HG group were significantly higher than those in NC group (P < 0.05). After transfection with miR-377-3p inhibitor, the levels of miR-377-3p, TGF-β, IL-6 and IL-18 in IN group were significantly decreased compared with HG group and MIN group. Conclusion: miR-377-3p expression was elevated both in serum of DKD patients and in HK-2 cells with high glucose induced injury, overexpression of miR-377-3p exacerbates the damage to HK-2 cells and promotes the progression of DKD. Silencing miR-377-3p can potentially regulate the levels of inflammatory factors in HK-2 cells by targeting downregulation of TGF-β expression, thereby mitigating the damage to HK-2 cells and delaying the development of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Cisplatin is still a widely used anticancer drug characterized by significant nephrotoxicity. Acute kidney injury (AKI), diagnosed based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, has limitations, including a delayed increase in creatinine. We determined the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in diagnosing AKI according to the KDIGO criteria in patients treated with cisplatin. We recruited 21 subjects starting cisplatin-based chemotherapy (Cisplatin-based group) and 11 treated with carboplatin-based chemotherapy or 5-fluorouracil regimens (non-cisplatin-based group). Blood and urine samples were collected during four subsequent cycles of chemotherapy (68 and 38 cycles, respectively). AKI occurred in four patients in the cisplatin-based group (5.9% of 68 cisplatin-based chemotherapy cycles). Among them, three urinary markers were increased by over 100% in two cases, two in one case and one in another. A doubling of at least one investigated parameter was observed more frequently during cisplatin-based chemotherapy (80.3% vs. 52.8%; OR = 3.65, 95% CI: 1.49–8.90; p < 0.01). The doubling of at least one new urinary AKI marker was more common in patients receiving cisplatin and frequently was not associated with overt AKI. Thus, a subclinical kidney injury detected by these markers occurs more frequently than deterioration in kidney function stated with creatinine changes. [ABSTRACT FROM AUTHOR]

Interleukin 18 (IL18) was originally identified as an inflammation-induced cytokine that is secreted by immune cells. An increasing number of studies have focused on its non-immunological functions, with demonstrated functions for IL18 in energy homeostasis and neural stability. IL18 is reportedly required for lipid metabolism in the liver and brown adipose tissue. Furthermore, IL18 (Il18) deficiency in mice leads to mitochondrial dysfunction in hippocampal cells, resulting in depressive-like symptoms and cognitive impairment. Microarray analyses of Il18−/− mice have revealed a set of genes with differential expression in liver, brown adipose tissue, and brain; however, the impact of IL18 deficiency in these tissues remains uncertain. In this review article, we discuss these genes, with a focus on their relationships with the phenotypic disease traits of Il18−/− mice. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP. Methods: Sprague–Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot saline and administered on the last day to produce nephrotoxicity via a single oral gavage at a dose of 1 g/kg. Kidney tissue samples were analyzed for human cartilage glycoprotein 39 (YKL-40), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), superoxide dismutase (SOD), and malondialdehyde (MDA). Data were subjected to one-way analysis of variance and the Wilcoxon rank-sum test Results: Renal tissue YKL-40, KIM-1, IL-18, and MDA levels in the APAP group were significantly higher than those in the control group (p < 0.05). The BA treatment completely restored renal KIM-1, YKL-40, and MDA levels and partially restored renal IL-18 and SOD levels in the rats subjected to renal damage induction (p < 0.05). The intertubular regions of rats administered with APAP had degeneration, necrosis, and infiltration of inflammatory cells and were immunopositive for IL-1 beta and 8-hydroxy-2′-deoxyguanosine. Conclusions: BA can be used in the prevention and replacement treatment of nephrotoxicity due to its inhibitory properties in multiple pathways and powerful antioxidant effects.

Background: The tumor microenvironment (TME) provides a conducive environment for the growth and survival of tumors. Negative factors present in TME, such as IL-10, may limit the effectiveness of cellular vaccines based on dendritic cells, therefore, it is important to control its effect. The influence of IL-10 on immune cells can be abolished e.g., by using antibodies against the receptor for this cytokine - anti-IL-10R. Furthermore, the anticancer activity of cellular vaccines can be enhanced by modifying them to produce proinflammatory cytokines, such as IL-12, IL-15 or IL-18. Additionally, an immunomodulatory dose of methotrexate and hydroxyethyl starch (HES-MTX) nanoconjugatemay stimulate effector immune cells and eliminate regulatory T cells, which should enhance the antitumor action of immunotherapy based on DC vaccines. The main aim of our study was to determine whether the HES-MTX administered before immunotherapy with anti-IL-10R antibodies would change the effect of vaccines based on dendritic cells overproducing IL-12, IL-15, or IL-18. Methods: The activity of modified DCs was checked in two therapeutic protocols - immunotherapy with the addition of anti-IL10R antibodies and chemoimmunotherapy with HES-MTX and anti-IL10R antibodies. The inhibition of tumor growth and the effectiveness of the therapy in inducing a specific antitumor response were determined by analyzing lymphoid and myeloid cell populations in tumor nodules, and the activity of restimulated splenocytes. Results and conclusions: Using the HES-MTX nanoconjugate before immunotherapy based on multiple administrations of anti-IL-10R antibodies and cellular vaccines capable of overproducing proinflammatory cytokines IL12, IL-15 or IL-18 created optimal conditions for the effective action of these vaccines in murine colon carcinoma MC38 model. The applied chemoimmunotherapy caused the highest inhibition of tumor growth in the group receiving DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg at the level of 72.4%. The use of cellular vaccines resulted in cytotoxic activity increase in both immuno- or chemoimmunotherapy. However, the greatest potential was observed both in tumor tissue and splenocytes obtained from mice receiving two- or threecomponent vaccines in the course of combined application. Thus, the designed treatment schedule may be promising in anticancer therapy. [ABSTRACT FROM AUTHOR]

The liver is in charge of a wide range of critical physiological processes and it plays an important role in activating the innate immune system which elicits the inflammatory events. Chronic ethanol exposure disrupts hepatic inflammatory mechanism and leads to the release of proinflammatory mediators such as chemokines, cytokines and activation of inflammasomes. The mechanism of liver fibrosis/cirrhosis involve activation of NLRP3 inflammasome, leading to the destruction of hepatocytes and subsequent metabolic dysregulation in humans. In addition, increasing evidence suggests that alcohol intake significantly modifies liver epigenetics, promoting the development of alcoholic liver disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, and DNA methylation are crucial in alcohol-evoked cell signaling that affects gene expression in the hepatic system. Though we are at the beginning stage without having the entire print of epigenetic signature, it is time to focus more on NLRP3 inflammasome and epigenetic modifications. Here we review the novel aspect of ALD pathology linking to inflammation and highlighting the role of epigenetic modification associated with NLRP3 inflammasome and how it could be a therapeutic target in ALD. [ABSTRACT FROM AUTHOR]

Objective: We investigated effects of serum serotonin and interleukin 18 levels on suicidal ideation (SI) at acute and chronic phases of acute coronary syndrome (ACS). Methods: Recent-onset 969 ACS patients were evaluated for serum serotonin and interleukin 18 levels; and SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. After 1-year, 711 patients were re-evaluated for SI. Logistic regression models were used adjustment for potential covariates. Results: Associations between serum interleukin 18 and SI at both phases were significant only in the lower serotonin group. Conclusion: By evaluating serum serotonin and interleukin 18 levels, the clinical prediction of SI of ACS may be improved. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP. Methods: Sprague-Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot saline and administered on the last day to produce nephrotoxicity via a single oral gavage at a dose of 1 g/kg. Kidney tissue samples were analyzed for human cartilage glycoprotein 39 (YKL-40), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), superoxide dismutase (SOD), and malondialdehyde (MDA). Data were subjected to one-way analysis of variance and the Wilcoxon rank-sum test Results: Renal tissue YKL-40, KIM-1, IL-18, and MDA levels in the APAP group were significantly higher than those in the control group (p < 0.05). The BA treatment completely restored renal KIM-1, YKL-40, and MDA levels and partially restored renal IL-18 and SOD levels in the rats subjected to renal damage induction (p < 0.05). The intertubular regions of rats administered with APAP had degeneration, necrosis, and infiltration of inflammatory cells and were immunopositive for IL-1 beta and 8-hydroxy-2'-deoxyguanosine. Conclusions: BA can be used in the prevention and replacement treatment of nephrotoxicity due to its inhibitory properties in multiple pathways and powerful antioxidant effects. [ABSTRACT FROM AUTHOR]

BackgroundThe tumor microenvironment (TME) provides a conducive environment for the growth and survival of tumors. Negative factors present in TME, such as IL-10, may limit the effectiveness of cellular vaccines based on dendritic cells, therefore, it is important to control its effect. The influence of IL-10 on immune cells can be abolished e.g., by using antibodies against the receptor for this cytokine - anti-IL-10R. Furthermore, the anticancer activity of cellular vaccines can be enhanced by modifying them to produce proinflammatory cytokines, such as IL-12, IL-15 or IL-18. Additionally, an immunomodulatory dose of methotrexate and hydroxyethyl starch (HES-MTX) nanoconjugate may stimulate effector immune cells and eliminate regulatory T cells, which should enhance the antitumor action of immunotherapy based on DC vaccines. The main aim of our study was to determine whether the HES-MTX administered before immunotherapy with anti-IL-10R antibodies would change the effect of vaccines based on dendritic cells overproducing IL-12, IL-15, or IL-18.MethodsThe activity of modified DCs was checked in two therapeutic protocols - immunotherapy with the addition of anti-IL10R antibodies and chemoimmunotherapy with HES-MTX and anti-IL10R antibodies. The inhibition of tumor growth and the effectiveness of the therapy in inducing a specific antitumor response were determined by analyzing lymphoid and myeloid cell populations in tumor nodules, and the activity of restimulated splenocytes.Results and conclusionsUsing the HES-MTX nanoconjugate before immunotherapy based on multiple administrations of anti-IL-10R antibodies and cellular vaccines capable of overproducing proinflammatory cytokines IL-12, IL-15 or IL-18 created optimal conditions for the effective action of these vaccines in murine colon carcinoma MC38 model. The applied chemoimmunotherapy caused the highest inhibition of tumor growth in the group receiving DC/IL-15/IL-15Rα/TAg + DC/IL-18/TAg at the level of 72.4%. The use of cellular vaccines resulted in cytotoxic activity increase in both immuno- or chemoimmunotherapy. However, the greatest potential was observed both in tumor tissue and splenocytes obtained from mice receiving two- or three-component vaccines in the course of combined application. Thus, the designed treatment schedule may be promising in anticancer therapy.

Immune-mediated rheumatic diseases (IMRDs), based on the leading mechanisms of pathogenesis, are conditionally classified into autoimmune, autoinflammatory, and «mixed pattern». In the spectrum of cytokines involved in the development of the immunopathological process in IMRDs, the “pro-inflammatory” cytokine interleukin (IL) 18, a member of the IL-1 family, plays an important role in the regulation of T-helper (Th) 1-, Th2- and Th17- types of immune response that induces the synthesis of interferon (IFN) γ, other pro-inflammatory cytokines and chemokines. The possibility of determining the concentration of IL-18 in IMRDs is discussed to improve diagnosis, identify subtypes of diseases, and predict the effectiveness of pharmacotherapy. IL-18 is a promising target for anticytokine therapy, primarily in patients with high activity of inflammation associated with hyperactivation of innate immunity.

Interleukin (IL)-18 is synthesized as a precursor that requires intracellular processing to become functionally active. In human, IL-18 is processed by caspase 1 (CASP1). In teleost, the maturation and signal transduction mechanisms of IL-18 are unknown. We identified two IL-18 variants, IL-18a and IL-18b, in turbot. IL-18a, but not IL-18b, was processed by CASP6/8 cleavage. Mature IL-18a bound specifically to IL-18 receptor (IL-18R) α-expressing cells and induced IL-18Rα—IL-18Rβ association. Bacterial infection promoted IL-18a maturation in a manner that required CASP6 activation and correlated with gasdermin E activation. The mature IL-18a induced proinflammatory cytokine expression and enhanced bacterial clearance. IL-18a-mediated immune response was suppressed by IL-18 binding protein (IL-18BP), which functioned as a decoy receptor for IL-18a. IL-18BP also functioned as a pathogen pattern recognition receptor and directly inhibited pathogen infection. Our findings revealed unique mechanism of IL-18 maturation and conserved mechanism of IL-18 signaling and regulation in turbot, and provided new insights into the regulation and function of IL-18 related immune signaling. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a common vascular disease, and pulmonary vascular remodeling is a pivotal pathophysiological mechanism of PAH. Major pathological changes of pulmonary arterial remodeling, including proliferation, hypertrophy and enhanced secretory activity, can occur in pulmonary artery smooth muscle cells (PASMCs). Multiple active factors and cytokines play important roles in PAH. However, the regulatory mechanisms of the active factors and cytokines in PAH remain unclear. The present study aimed to reveal the crucial role of PASMC pyroptosis in PAH and to elucidate the intrinsic mechanisms. To establish the PAH rat models, Sprague-Dawley rats were injected intraperitoneally with monocrotaline (MCT) at a dose of 60 mg/kg. The expression of proteins and interleukins were detected by western blotting and ELISA assay. The results indicated that the pyroptosis of PASMCs is significantly increased in MCT-induced PAH rats. Notably, pyroptotic PASMCs can secret IL-1β and IL-18 to promote the proliferation of PASMCs. On this basis, inhibiting the secretion of IL-1β and IL-18 can markedly inhibit PASMC proliferation. Collectively, the findings of the present study indicate a critical role for PASMC pyroptosis in MCT-induced PAH rats, prompting a new preventive and therapeutic strategy for PAH. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.

We aimed to determine the genetic polymorphisms and serum level of interleukin 18 in Fars ethnic groups. 226 Fars ethnic groups were participated. The ATP III criteria were used to assess MS components. The SNPs of the IL-18 gene were determined with ARMS-PCR. The GG, GC, and CC genotypes of −137 were 50%, 40%, and 10%. The CC, CA, and AA genotypes of −607 were 45%, 37%, and 18%. The GG, GC, and CC genotypes of −137 were 44.20%, 43.40%, and 12.40%, and were 55.75%, 36.28%, and 7.97% in subjects with and without MS, respectively. The CC, CA, and AA genotypes of −607 were 48.70%, 37.20%, and 14.20% and were 41.60%, 37.20%, and 21.20% in both groups, respectively. IL-18 gene may different in specific populations, different ethnic groups and geographic regions. The IL-18 polymorphisms might not be used as a marker of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by immune system dysfunction, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting from excessive accumulation of extracellular matrix (ECM) elements, including collagen and proteoglycans (PGs). An uncontrolled PG proliferation, caused by disturbances in their metabolism in tissues, is most likely reflected in the quantitative changes of their components, i.e., glycosaminoglycans (GAGs), in body fluids. Therefore, the aim of this study was to quantify the different types of GAGs in the blood and urine of systemic sclerosis patients. Chondroitin/dermatan sulfates (CS/DS) and heparan sulfates/heparin (HS/H) were quantified by hexuronic acid assay and electrophoretic fractionation, while hyaluronic acid (HA) and keratan sulfates were evaluated using ELISA tests. In turn, individual urinary GAGs were determined using the Blyscan™ Sulfated Glycosaminoglycan Assay Kit. Our results showed that the plasma concentrations of CS/DS, HS/H, HA, and KS in systemic sclerosis patients were significantly higher compared with those in healthy subjects. In the case of urine measurements, we have found that in SSc patients, CS/DC concentrations were significantly higher, while HA concentrations were significantly lower compared with the values observed in the urine of healthy subjects. Importantly, the found by us correlations between plasma keratan sulfate levels and both the duration of the disease and the severity of skin lesions, as expressed by the Rodnan scale, seems to suggest this GAG as a potential marker in assessing disease progression and activity. In addition, a level of urinary excretion of all types of GAGs due to their high positive correlation with uACR, may be a valuable complementary test in the diagnosis of early renal dysfunction in the course of SSc. [ABSTRACT FROM AUTHOR]

Background: The end stage of chronic liver disease (CLD) is cirrhosis, which is characterised by progressive scarring (fibrosis) of the liver due to chronic liver injury and subsequent loss of liver function. Early diagnosis and prevention of complication of liver cirrhosis is challenging, so Interleukin-18 is one of the surrogate serum indicators being investigated for noninvasive evaluation of liver fibrosis. The interferon-gamma inducing factor IL-18 plays a crucial role in the development of chronic liver disease by promoting inflammation. However, its precise role is unclear due to a paucity of data. Objective: Assessment of possible correlation between Interleukin 18 and liver cirrhosis. Methods: Interleukin 18, hepatitis, and liver cirrhosis were all looked for in PubMed, Google scholar, and Science direct. References from relevant literature were also evaluated by the authors, but only the most recent or complete study from January 2000 to May 2020 were included. Due to the lack of sources for translation, documents in languages other than English have been ruled out. Papers that did not fall under the purview of major scientific investigations, such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations, were omitted. Conclusion: IL-18 plays a pathogenic role in liver cirrhosis as well as portal hypertension development and may represent non-invasive marker for HCV related cirrhosis. [ABSTRACT FROM AUTHOR]

Aim. To establish the effect of experimental intra-abdominal hypertension (IAH) on the teeth-jaw system of rats in the long-term period based on the study of pro-inflammatory cytokines and morphological analysis of the elements of the temporomandibular joint (TMJ) and salivary glands.Materials and methods. The experiment was carried out on 60 newborn rats; IAH was modelled by injecting collagen into the abdominal cavity to a predetermined level of intra-abdominal pressure. The rats were evenly (n = 20) divided into 3 groups: 1st - control; 2nd and 3rd - with light and severe IAH, respectively. Serum levels of IL-18, MCP-1, NGAL were determined by multiplex analysis after 10 and 120 days, VEGF-C - after 10 days - by ELISA. The morphological examination of the TMJ and salivary glands was performed using a Leica DM2000 microscope after 120 days.Results. After 10 days and 120 days, blood serum levels of NGAL, IL-18 and MCP-1 were statistically significantly increased in groups 2 and 3 compared to the control; the concentration of MCP-1 increased in proportion to the severity of the IAH with the maximum values in group 3. After 10 days, the level of VEGF was significantly increased in group 2 compared to the control group (p < 0.02). Inflammation of the TMJ was observed significantly more often in groups 2 and 3 than in the control group (p = 0.0002). In group 3, circulatory disorders and bone marrow degeneration of the TMJ, as well as inflammation, circulatory disorders and hyperplasia of the lymphoid tissue of the salivary glands were statistically significantly more often compared to groups 1 and 2.Conclusion. In the long term, experimental IAH showed an increase in the levels of markers of inflammation and hypoxia in the blood serum of rats; the severity of synovitis and sialadenitis grew with an increase in the level of intra-abdominal pressure; the maximum deviations in inflammation markers and morphological changes in the TMJ and salivary glands of rats were observed in the group with severe IAH.

Abstract The inflammasome is a cytosolic multiprotein complex that plays a crucial role in inflammation and cell death. The sensor proteins in the inflammasome complex detect various microbial and endogenous stimuli, leading to subsequent caspase activation. The activation of caspases results in the maturation of pro‐inflammatory cytokines IL‐1β and IL‐18 or pyroptosis. Inflammasome dysfunction is associated with the pathogenesis of various diseases, including autoimmune disease and cancer. It appears that the interactions between the gut microbiota and the inflammasome play crucial roles in the gastrointestinal tract. The gut microbiota induces the expression and activation of inflammasome proteins, which contribute to both homeostasis and disease in the gut. Likewise, although controversial, mounting evidence suggests that inflammasome activation can modulate the composition of the gut microbiota, which, in turn, affects disease progression. In this review, we summarize the current concepts and recent insights linking the inflammasome and gut commensal microorganisms. We describe how the reciprocal interaction between the inflammasome and the commensal microbiota relates to physiological and pathophysiological consequences in the host.

Background: Gasdermin D (GSDMD) plays an essential role in the pathway of pyroptosis. However, whether GSDMD participates in myocardial ischaemia/reperfusion injury (MI/RI) remains poorly understood. Methods: Serum levels of GSDMD and IL-18 in ST-segment elevation myocardial infarction (STEMI) patients were measured by ELISA. The expression of GSDMD and GSDMD N-terminal (GSDMD-NT) in vivo and in vitro was assessed by western blot and immunofluorescence staining. GSDMD-/- mice and wild type (WT) mice were induced MI/RI, followed by cardiac ultrasound and histological analysis. Results: Clinically, patients suffering from STEMI after percutaneous coronary intervention (PCI) exhibited higher levels of GSDMD and IL-18 than that in the controls. In vitro, the cleavage of GSDMD was significantly upregulated in macrophages exposed to hypoxia/reoxygenation or H2O2. In vivo, the levels of GSDMD and GSDMD-NT increased notably after MI/RI, especially in macrophages infiltrating in the infarct area. Moreover, compared with WT mice, GSDMD-/- mice showed reduced infarct size (25.45 ± 3.07% versus 36.47 ± 3.72%), improved left ventricular ejection fraction (37.71 ± 1.81% versus 29.44 ± 2.28%) and left ventricular fractional shortening (18.01 ± 0.97% versus 13.62 ± 1.15%) as well as attenuated pathological damage after I/R injury, along with reduced levels of proinflammatory cytokines and decreased infiltration of neutrophils. Conclusions: Our study revealed that GSDMD deficiency significantly alleviated the inflammatory response by regulating pyroptosis, reduced the infarct size and preserved cardiac function after MI/RI, thus providing a potential strategy for the treatment of myocardial reperfusion injury. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) are Gram-positive bacteria which are considered for use as adjuvant therapeutics in management of various disease ailments, including obesity, irritable bowel syndrome, lactose intolerance and cancer. To investigate the possible use of Lactococcus lactis strains from our collection in treatment of gastrointestinal cancer, we tested them for the ability to arrest proliferation of human colorectal adenocarcinoma cells (Caco-2). Results of the BrdU assay showed that the anti-proliferative activity of L. lactis cells is strain-specific. We found that particularly, two strains, L. lactis IBB109 and L. lactis IBB417, exhibited the most potent inhibitory effect. Moreover, both strains triggered interleukin 18 gene expression, normally inhibited in Caco-2 (cancer) cells. To examine the probiotic potential of the two strains, we tested them for bile salts and acid tolerance, as well as adhesion properties. Both isolates exhibited probiotic potential—they survived in the presence of 0.3% bile salts and tolerated exposure to low pH and osmotic stress. Notably, we found that L. lactis IBB417 displayed better adherence to mucus and Caco-2 cells than L. lactis IBB109. Additionally, by microdilution tests we confirmed that both strains are sensitive to all nine antibiotics of human and veterinary importance listed by the European Food Safety Authority. Finally, by in silico investigations of whole genome sequencing data, we revealed the genetic features of L. lactis IBB109 and L. lactis IBB417 that can be associated with functional (e.g., adhesion and carbohydrate metabolic genes) and safety (e.g., virulence and antibiotic resistance) aspects of the strains, confirming their health-promoting potential. [ABSTRACT FROM AUTHOR]

Background and Objectives: The formation and destabilization of atherosclerotic plaques is a complex process involving several proteins and cytokines. Interleukin 6 (IL-6), interleukin 18 (IL-18), and tumor necrosis factor (TNF-α) are examples of such cytokines. The goal of our research is to compare the concentrations of the above-mentioned indicators in the plasma of patients with verified high-risk atherosclerotic plaque to the plasma levels of healthy people before lipid lowering therapy. Materials and Methods: Patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography were included in the study. The concentrations of IL-6, IL-18 and TNF-α in the plasma of these people were determined and compared with the concentrations of these cytokines in the plasma of the control group. Results: Levels of lipid panel, IL-6 and IL-18 were significantly lower in the group of healthy people than in the study group. Conclusions: The concentrations of IL-6 and IL-18 in the plasma of patients with ruptured plaque are higher than in the plasma of healthy people, suggesting that these cytokines as a panel might be used as new indicators of the presence of unstable atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the association of IL‐18 137 G > C, 607 C > A gene polymorphism in Uyghur population with chronic periodontitis (CP) and combine the results with the meta-analysis In a case‐control study, 200 cases with CP and 100 healthy controls were recruited; IL‐18 137 G > C, 607 C > A genotyping was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). In the meta‐analysis, we used electronic databases, including CNKI, Wan Fang, PubMed, EMBASE databases etc.to obtain relevant research published through June 2020. Studies were considered eligible if odds ratios (ORs) and 95% confidence intervals (95% CI) were provided or calculated from the given data. The size of the combined effect was calculated using STATA 15.0 Our study revealed significant association between CP and IL‐18 137 G > C (P =.045, OR = 1.67), 607 C > A (P =.045, OR = 1.67). The overall meta‐analysis revealed significant associations between IL‐18 137 G > C polymorphism and CP risk in Allele, dominant, co-dominant and recessive genetic models. The subgroup analysis also showed a significant association between the IL‐18 137 G > C and risk for periodontitis and aggressive periodontitis in the Asian (GC+ CC VS. GG: P =.047, OR = 1.64,95%CI = 1.01–2.68) IL‐18 137 G > C, 607 C > A could be associated with susceptibility to periodontitis in Uyghur population. Further case-control of candidate genes studies targeting larger sample sizes and different ethnic groups are needed to arrive more accurate conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Inflammasomes are multiprotein complexes, which regulate proinflammatory cytokines, Interleukin-18 (IL-18), and Interleukin-1β (IL-1β) that are associated with periodontal breakdown. This study investigated the expression of NOD-like receptor pyrin domain-containing-3 (NLRP3) and NOD-like receptor family CARD domain-containing protein 4 (NLRC4) inflammasomes in different periodontal diseases in humans and their potential association with IL-18 release in gingival crevicular fluid (GCF). Materials and Methods: A total of 45 participants (21 males and 24 females) divided into four groups; periodontally healthy (H), gingivitis (G), chronic periodontitis (CP), and aggressive periodontitis (AgP) based on periodontal examination. NLRC4 and NLRP3 expression were detected by immunohistochemistry in gingival tissue samples for all groups. Expression percentage (%) and staining intensity distribution score (SID) were calculated for both NLRC4 and NLRP3. IL-18 was measured in GCF via enzyme linked immunosorbent assay (ELISA). Results: Positive immunoreactivity was seen for NLRC4 and NLRP3 across groups. No differences were found for NLRC4 expression %, but SID scores were slightly higher in G and AgP compared to other groups (P > 0.05). Results showed a significant increase of NRLP3 expression % in group CP compared to group H (P < 0.05) without affecting SID scores (P > 0.05). IL-18 levels were significantly higher in AgP and CP groups compared to H and G groups (P < 0.05). IL-18 significantly and positively correlated with clinical attachment levels across groups. Conclusion: Within the limitations of this preliminary study, we suggest that the NLRC4 platform may have a protective role contrary to the NLRP3 platform influencing IL-18 release and associated periodontal tissue breakdown.

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage.

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68+ cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immune responses and cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background: The purpose of the present study was to investigate the age- and gender-related serum level of interleukin 18 (IL18) in male and female Iranian Fars ethnic group with metabolic syndrome components. Methods: The study included 226 native Iranian Fars ethnic groups. One hundred sixteen females and 110 men were selected. There were 60 females and 50 males with metabolic syndrome and 56 females and 60 males without metabolic syndrome. The serum fasting blood glucose (FBS), lipid profiles, and IL18 were measured. The National Cholesterol Education Program Adult treatment Panel III criteria were used to determine metabolic syndrome components. Results: There were significant differences between the males and females [except high-density lipoprotein (HDL)] with and without metabolic syndrome for the mean body mass index, FBS, HDL-cholesterol, waist circumference (WC), triglyceride (TG), and IL18 levels in all age groups. Serum IL18 was the highest in males and females in age groups 61–70 and 41–50 years with metabolic syndrome, respectively. Serum IL18 levels significantly correlated with TG and waist WC in males (and also correlated with HDL) and females with the metabolic syndrome. There were significant correlations between IL18 and TG and WC in males (and also correlated with HDL) in ages 61–70 years and females in ages 41–50 years with the metabolic syndrome. Conclusions: The increased IL18 level in both gender and different ages may have an important role in the alteration of some metabolic syndrome components. These alterations may be made to happen in different related metabolic diseases. IL18 seems to be a useful biomarker for the management of metabolic syndrome components and the risk factors of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: The Pathological symptoms of Alzheimer’s disease and the degeneration of nerve cells cause inflammation in these patients. This study aimed to investigate the effect of endurance training and saffron extract on the plasma levels of interleukin 17 and 18 in Alzheimer’s rats by trimethyltin chloride. Methods: This experimental study was conducted on 32 male Sprague-Dawley rats weighing 180 ± 20 grams. After Alzheimer’s induction (by the intraperitoneal injection of 80 mg/kg trimethyltin chloride), the rats were randomly assigned into four groups: control, training, saffron extract, saffron extract + training. The saffron extract was injected intraperitoneally at the dose of 25 mg/kg, daily, for eight weeks. Also, the endurance training program consisted of incremental running on the treadmill at a speed of 15 to 20 m/min. The program was performed in 15 to 30 minutes sessions, three sessions per week, for eight weeks. Finally, the obtained data were analyzed using two-way ANOVA at the P < 0.05. Results: The results showed that exercise (P=0.10), saffron consumption (P=0.07), and the interaction of exercise and saffron consumption (P=0.06) did not significantly affect interleukin 17, in rats. Also, exercise (P=0.68), saffron consumption (P=0.84), and the interaction of exercise and saffron consumption (P=0.57) had no significant effect on interleukin 18, in rats. Conclusion: According to the results, it seems that exercise training and saffron extract do not affect the interleukin 17 and interleukin 18 in Alzheimer’s rats.

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68+ cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immune responses and cardiotoxicity.

Autoinflammatory diseases (AIDs) are conditions characterized by dysfunction of innate immunity, causing systemic inflammation and various clinical symptoms. The field of AIDs has expanded due to improved comprehension of pathophysiological mechanisms and advancements in genomics techniques. A new emerging category of AIDs is characterized by a significant increase in interleukin 18 (IL-18), a pro-inflammatory cytokine synthesized in macrophages and activated by caspase 1 via various inflammasomes. IL-18 plays a role in the regulation of innate and adaptive immunity. IL-18 is involved in various functions, such as the proliferation, survival, and differentiation of immune cells, tissue infiltration of immune cells, polarization of immune responses, and production of other pro-inflammatory cytokines. This review analyzes the literature on IL-18 regarding its functions and its implications in the diagnosis and treatment of AIDs. IL-18-associated AIDs comprise Still's disease and diseases associated with mutations in NLRC4, XIAP, CDC42, and PSTPIP1, as well as IL-18BP deficiencies. With the exception of PSTPIP1-associated diseases, these conditions all carry a risk of macrophagic activation syndrome. Measuring IL-18 levels in serum can aid in the diagnosis, prognosis, and monitoring of these diseases. Therapies targeting IL-18 and its signaling pathways are currently under investigation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

The inflammasome is a cytosolic multiprotein complex that plays a crucial role in inflammation and cell death. The sensor proteins in the inflammasome complex detect various microbial and endogenous stimuli, leading to subsequent caspase activation. The activation of caspases results in the maturation of pro‐inflammatory cytokines IL‐1β and IL‐18 or pyroptosis. Inflammasome dysfunction is associated with the pathogenesis of various diseases, including autoimmune disease and cancer. It appears that the interactions between the gut microbiota and the inflammasome play crucial roles in the gastrointestinal tract. The gut microbiota induces the expression and activation of inflammasome proteins, which contribute to both homeostasis and disease in the gut. Likewise, although controversial, mounting evidence suggests that inflammasome activation can modulate the composition of the gut microbiota, which, in turn, affects disease progression. In this review, we summarize the current concepts and recent insights linking the inflammasome and gut commensal microorganisms. We describe how the reciprocal interaction between the inflammasome and the commensal microbiota relates to physiological and pathophysiological consequences in the host. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a skin disease affecting 2.3% of the Iraqi population and begins as a local disease with subsequent systemic comorbidities. Aim: The aim was to clarify whether psoriasis is a local or systemic disease. Materials and Methods: A total of 211 subjects with psoriasis and 163 sex- and age-matched controls were included in the study. Serum adiponectin, interleukin-6, interleukin-8, interleukin-10 (IL-10), interleukin-23 (IL-23), interleukin-18 (IL-18), paraoxonase, lipoprotein (a), osteopontin, chemerin, tumor necrosis factor-α (TNF-α), high-sensitivity C- reactive protein (hs-CRP), bilirubin, D-dimer, and creatinine were determined using commercial kits. Results: There was no significant difference in the mean age and BMI between psoriasis and the control groups. However, there was significantly higher mean serum values of IL-6, IL-8, IL-10, IL-23, lipoprotein (a), chemerin, TNF-α, hs-CRP, osteopontin, D-dimer, troponin I, creatinine, bilirubin, and platelet counts in psoriatic patients than in the controls. Meanwhile, the serum mean values of adiponectin, paraoxonase, and cortisol were significantly lower in psoriasis subjects than in the controls. The mathematical model was proposed to clarify whether psoriasis is a systemic or local disease. The application of the model to our data of biomarkers indicated the presence of systemic inflammation in psoriasis. Conclusion: The present study finding suggests that psoriasis is a systemic disease rather than a local skin disease. However, there is a need for the application of the model in a large-scale study. [ABSTRACT FROM AUTHOR]

BackgroundThe interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear.Study designPost hoc analysis of prospective cohort study.Setting & participantsThe 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants.PredictorUnadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery.OutcomeAKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI).MeasurementsStratified analyses by preoperative estimated glomerular filtration rate (eGFR) ≤ 60 versus > 60mL/min/1.73m(2).Results180 (42%) patients with preoperative eGFRs≤60mL/min/1.73m(2) developed clinical AKI compared with 246 (31%) of those with eGFRs>60mL/min/1.73m(2) (P

Aim: It has been observed that patients with type 2 diabetes mellitus have impaired balance between pro inflammatory and anti infalammatory markers as well as an imbalance between toxic and essential trace metals. The purpose of this research therefore is to assess the levels lead, chromium and serum interleukin-18 levels in type 2 diabetics. Methods: Thus, a total of 110 patients were investigated -- 40 were either newly diagnosed with type 2 diabetes mellitus or had been previously diagnosed but had stopped treatment for at least 10weeks and currently not on drugs, 40 with type 2 diabetes mellitus and on treatment for at least six weeks, and 30 control subjects with normal plasma glucose level. Plasma glucose level, blood lead level, chromium and copper levels and serum interleukin 18 levels were estimated in all groups. Results: Plasma glucose and serum interleukin 18 levels was significantly high in treated diabetics than in control (P<0.05), blood chromium was significantly higher in control than in treated diabetics (P<0.05), BMI and blood lead levels were insignificantly higher in treated diabetics than in control (P<0.05). In untreated diabetics, plasma glucose, blood lead, serum interleukin-18 and BMI were significantly higher while blood chromium and copper was significantly lower than control (P<0.05). When treated and untreated diabetics were compared, plasma glucose, blood lead and copper, serum interleukin 18 and BMI was significantly higher in the untreated group while blood chromium level was significantly higher in treated diabetics (P<0.05). Conclusion: It appears that serum interleukin 18- a pro inflammatory cytokine is higher in diabetes subjects and can be significantly lowered through the intake of antidiabetic drugs, essential metal supplementation and lifestyle modifications over a period of time. This is because, in this research, serum interleukin 18, Lead and Copper levels nosedived with a reduction in plasma glucose levels. This area of study requires further investigation with other antidiabetic drugs. This, on the long run might be economically helpful in designing better and economic treatment protocols with a possibility of better clinical outcomes. [ABSTRACT FROM AUTHOR]

BackgroundKidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure.Study designRetrospective cohort study.Setting & participants2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort.PredictorsRatios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively).OutcomesIncident heart failure over a median follow-up of 12 years.ResultsMedian values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51).LimitationsGeneralizability to other populations is uncertain.ConclusionsHigher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.

This study investigated changes in the concentrations of serum and urine neutrophil gelatinase lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and cystatin-C (Cys-C) induced by parenchymal and tubular damage following blunt kidney trauma, as well as their potential utility as biomarkers in the detection and follow-up of patients with suspected blunt renal trauma. Three-month-old male Sprague-Dawley rats (n = 18) were divided into three groups (n = 6 in each): group 1: control group (no intervention); group 2: sham group (explorative surgery and exposure of the left kidneys); and group 3: trauma group (explorative surgery and induction of blunt renal trauma of the left kidneys). Serum and urine samples were collected before and 12-24, 36-48, and 60-72 hours later for NGAL, KIM-1, IL-18, and Cys-C measurements. In the trauma group, there was a statistically significant increase in post-operative NGAL, KIM-1, and IL-18 values after 12-24 h and 36-48 h, as compared with pre-operative values. There was also a statistically significant increase in post-operative serum and urine Cys-C values after 60-72 h, as compared with pre-operative values. NGAL, KIM-1, and IL-18 may represent novel non-invasive descriptive candidate biomarkers of early-stage tubular damage in children with renal trauma.

Introduction: Metabolic syndrome is a common clinical anomaly, with an increased risk of developing type 2 diabetes and cardiovascular risk factors. Increased inflammatory mediators, such as reactive protein,as well as the inflammatory cytokines can be associated with the incidence and progression of metaboli syndrome and type 2 diabetes. Materials & Methods: This study was performed on 35 male and female patients with an average age of 55 years, type 2 diabetes mellitus with metabolic syndrome and 35 healthy subjects as control group. Separated serum samples were kept at -20 ° C for quantitative evaluation of serum IL-18 by ELISA kit and C-reactive protein. RNA extraction from cells was performed by JenaBioscience kit and finally Gene expression assay was performed quantitatively using Real Time RTPCR. Findings: The mean serum levels of IL-18 were significantly increased (P=0.008), and serum reactive protein (P

Introduction: By aging population, the heart failure and its life-threatening complications have become an enormous issue in public health. Regarding the inflammation as a major contributing pathological factor, the determination of most important inflammatory targets for immunomodulation is a problematic puzzle in the treatment of heart failure patients and the inflammatory pathways primarily involved in different underlying conditions contributing to heart failure can be an area which is worthy of focused research. Considering the dilated cardiomyopathy (DCM) as a relatively high-incident disease leading to heart failure, the aim of this study is to determine the difference in the expression level of interleukin (IL)-6 and IL-18 in patients with ischemic and idiopathic DCM. Methods: 39 non-diabetic patients with ischemic and 37 ones with idiopathic DCM were enrolled in the study. 48 healthy individuals were also considered as control group. For quantitative determination of the mRNA expression level of IL-6 and IL-18 genes, an in-house- SYBR Green real-time PCR was used and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was considered as internal control gene. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) was calculated by 2D echocardiographic assessment. Data were finally analyzed via SPSS statistical software version 19.0 using independent t test and 2-∆∆Ct method and P

Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) from age-matched T1D and control children using flow cytometry. We observed that CD8 and DN MAIT cell frequencies were similarly abundant between the two groups. We tested for associations between MAIT cell frequency and T1D-associated parameters, which could reveal a pathogenic role for MAIT cells in the absence of changes in frequency. We found no significant associations between CD8 and DN MAIT cell frequency and levels of islet cell autoantibodies (ICA), glutamate decarboxylase 65 (GAD65) autoantibodies, zinc transporter 8 (ZNT8) autoantibodies, and insulinoma antigen 2 (IA-2) autoantibodies. Furthermore, CD8 and DN MAIT cell frequencies were not significantly associated with time since diagnosis, c-peptide levels, HbA1c, and BMI. As we have examined this cohort for multiple soluble factors previously, we tested for associations between relevant factors and MAIT cell frequency. These could help to explain the broad range of MAIT frequencies we observed and/or indicate disease-associated processes. Although we found nothing disease-specific, we observed that levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were all associated with MAIT cell frequency. Finally, previous cytomegalovirus infection was associated with reduced CD8 and DN MAIT cells. From this evaluation, we found no connections between CD8 and DN MAIT cells and children with T1D. However, we did observe several intrinsic and extrinsic factors that could influence peripheral MAIT cell abundance among all children. These factors may be worth consideration in future experimental design.

Background and Objectives: The formation and destabilization of atherosclerotic plaques is a complex process involving several proteins and cytokines. Interleukin 6 (IL-6), interleukin 18 (IL-18), and tumor necrosis factor (TNF-α) are examples of such cytokines. The goal of our research is to compare the concentrations of the above-mentioned indicators in the plasma of patients with verified high-risk atherosclerotic plaque to the plasma levels of healthy people before lipid lowering therapy. Materials and Methods: Patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography were included in the study. The concentrations of IL-6, IL-18 and TNF-α in the plasma of these people were determined and compared with the concentrations of these cytokines in the plasma of the control group. Results: Levels of lipid panel, IL-6 and IL-18 were significantly lower in the group of healthy people than in the study group. Conclusions: The concentrations of IL-6 and IL-18 in the plasma of patients with ruptured plaque are higher than in the plasma of healthy people, suggesting that these cytokines as a panel might be used as new indicators of the presence of unstable atherosclerotic plaque.

Background: Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied.Objective: To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms.Methods: Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries.Results: Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and <.001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03).Limitations: Cohort was small.Conclusion: Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity. [ABSTRACT FROM AUTHOR]