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Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder accompanied by skin eruption. However, typical skin eruptions, such as evanescent, salmon-pink erythema, are not specific to AOSD and dermatologists often face difficulty in diagnosing AOSD. In this study, we examined serum IL-18 levels as well as IL-6, ferritin and C-reactive protein in 6 Japanese patients with AOSD.Serum levels of IL-6 and IL-18 were evaluated in the acute phase and at the time of remission. Serum levels of IL-6 were analyzed using a commercial chemiluminescent enzyme immunoassay (CLEIA; SRL, Tokyo, Japan). Serum IL-18 levels were measured using a commercial ELISA kit (MedicalBiological Laboratories Co., LTD. Nagoya, Japan).In active AOSD, serum ferritin levels and CRP levels were above normal range in 6 patients. In remission, serum ferritin levels of 3 patients were slightly above the normal range, while CRP serum levels of 6 patients were all normalized. Serum IL-18 levels were markedly elevated in 5 cases during the acute phase. In remission, serum IL-18 levels remained at higher values than the normal range in 5 cases. Serum IL-6 levels were also highly elevated in 5 patients in active AOSD and became normalized in remission except in case 2.High levels of serum IL-18 will be a clue to the diagnosis of AOSD. CRP is also useful biomarker for monitoring disease activity compared with IL-6 and IL-18.

Purpose: To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. Methods: A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. Results: The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p

OBJECTIVE To compare the effect of ursodesoxycholic acid (UDCA) with S-adenosyl-L-methionine (SAMe) plus UDCA in handling of cholestasis in neonates, and their influences on serum endotoxin, matrix metalloproteinase-9 (MMP-9) and interleukin 18 (IL-18). STUDY DESIGN Randomised controlled trial. PLACE AND DURATION OF STUDY Luzhou People's Hospital, China, from April 2019 to December 2020. METHODOLOGY A total of 102 neonates with cholestasis were evenly divided into control group and observation group with random double-blind. The former treated with UDCA tablets, and the latter was treated with SAMe plus UDCA. Serum endotoxin, MMP-9 and IL-18 were compared between the two groups. RESULTS Total effective rate of treatment in observation group was 92.16% (47 cases), which was higher than that in control group 70.59% (36 cases) (p=0.005). Levels of serum endotoxin, MMP-9 and IL-18 in observation group were respectively 11.12 ± 1.07 pg/mL, 646.72 ± 42.56 ng/mL and 2.51 ± 0.19 pg/mL, which was lower than those in control group (p

Pneumonia is currently one of the leading causes of death in children. Increased susceptibility to pneumonia may be due to their decreased immunity. One of the reasons for the decrease in immunity is zinc deficiency. In children with pneumonia, on the other hand, some cytokines are secreted, resulting in inflammation that spreads, persists, and makes treatment difficult for specialists. In this study, we investigated the serum zinc level in children with pneumonia and healthy children. Also, we tried to find its relationship with IL-18 mRNA expression as an inflammatory cytokine. For this purpose, serum zinc levels and IL-18 mRNA expression were evaluated in 120 children aged 3-60 months with pneumonia and 120 healthy children. After taking 2ml of blood from children and measuring serum zinc level, the level of the IL-18 mRNA was measured by real-time PCR. Total RNA was extracted by bioZOL™-G RNA Isolation Reagent kit. The primary cDNA was amplified by the extracted RNA, and in the next step, 2µl of cDNA were amplified by specific primers to measure IL-18 mRNA. The Beta-actin gene was also used as internal control and housekeeping gene. Results showed that the level of zinc in the patient group was 412.625±28.87?M and in the control group was 514.40±49.67?M. This difference was statistically significant (P=0.0053). Also, the expression of the IL-18 gene was increased in children with pneumonia, significantly (P=0.0015). Therefore, from the results, it can be deduced that children with zinc deficiency were at higher risk for a lung infection. Inflammatory cytokines such as IL-18 also were increased in these children. Hence, it can be concluded that zinc levels can reduce the expression of IL-18 mRNA and play an important role in the prevention and treatment of children with pneumonia.

Infection, particularly prenatal infection leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes in the prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviors through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-1β, IL-6, TNF-α and IL-17A assessed after 24 hours were observed in poly (I:C) and LPS-treated rats, indicating MIA. The offspring rats of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviors, deficits in social behaviors and prepulse inhibition. The hippocampus of offspring rats showed increased expression of TLR3, TLR4, NLRP3, IL-1β, and IL-18 of poly (I:C) and TLR3, TLR4, NLRP3, Cas1, IL-1β, and IL-18 of LPS-treated dams. Notably, the expression of these genes showed a positive correlation with apoptotic and a negative correlation with neuroprotective genes. Furthermore, TLR and inflammasome genes had significant impact on social deficits and impaired prepulse inhibition in offspring rats. The results suggest MIA due to prenatal infection perhaps trigger TLR, inflammasome and apoptotic pathways leading to the induction of schizophrenia-like behaviors in the later stages of life. Prenatal infections seem to drive neuroprogression and subsequently schizophrenia-like symptoms through a common central pathway involving TLR, inflammasome and apoptosis.

Rationale: Primary graft dysfunction (PGD) is a severe form of acute lung injury, leading to increased early morbidity and mortality after lung transplant. Obesity is a major health problem, and recipient obesity is one of the most significant risk factors for developing PGD. Objectives: We hypothesized that T-regulatory cells (Tregs) are able to dampen early ischemia–reperfusion events and thereby decrease the risk of PGD, whereas that action is impaired in obese recipients. Methods: We evaluated Tregs, T cells, and inflammatory markers, plus clinical data, in 79 lung transplant recipients and 41 liver or kidney transplant recipients and studied two groups of mice on a high-fat diet (HFD), which did (“inflammatory” HFD) or did not (“healthy” HFD) develop low-grade inflammation with decreased Treg function. Measurements and Main Results: We identified increased levels of IL-18 as a previously unrecognized mechanism that impairs Tregs’ suppressive function in obese individuals. IL-18 decreases levels of FOXP3, the key Treg transcription factor, decreases FOXP3 di- and oligomerization, and increases the ubiquitination and proteasomal degradation of FOXP3. IL-18–treated Tregs or Tregs from obese mice fail to control PGD, whereas IL-18 inhibition ameliorates lung inflammation. The IL-18–driven impairment in Tregs’ suppressive function before transplant was associated with an increased risk and severity of PGD in clinical lung transplant recipients. Conclusions: Obesity-related IL-18 induces Treg dysfunction that may contribute to the pathogenesis of PGD. Evaluation of Tregs’ suppressive function together with evaluation of IL-18 levels may serve as a screening tool to identify obese individuals with an increased risk of PGD before transplant.

AIM: The study aimed to assess the effectiveness of alloferon in human papillomavirus (HPV)-associated cervical neoplasia (grade I) based on the analysis of the cytokine profile in cervical mucus as well as markers of apoptosis in cervical epithelial cells. MATERIALS AND METHODS: The study enrolled 98 women, including 55 women of reproductive age with cervical intraepithelial neoplasia (CIN) associated with HPV infection and 43 conditionally healthy women without HPV infection. Factors of cytokine response and markers of apoptosis under normal and pathology conditions were assessed and compared. RESULTS: The imbalance of pro-inflammatory and anti-inflammatory cytokines, in favor of the latter, is an important factor that supports the persistence of HPV-associated grade I CIN. Reducing caspase-3 and caspase-9, increasing interleukin-18, and subsequent activation of interferon gamma against the background of alloferon use are favorable signs of substantial elimination of the HPV. CONCLUSIONS: The results of this study show considerable elimination of HPV in patients with grade I CIN when using immunological antivirus therapy.

Cobalt is a dermal sensitizer, and keratinocytes respond to cobalt exposure by releasing proinflammatory mediators, regulating the immune response.To determine the effect of cobalt on the inflammas...

The purpose of our study is to investigate the roles of IL-18 gene variations in bladder cancer development in Thrace population of Turkey. This study was carried out with 103 bladder cancer patients and 81 healthy controls. Genotype distributions of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations were determined using polymerase chain reaction (PCR) method. The CC homozygous genotype for IL-18 (-607 C/A) gene variation was significantly higher in patients with bladder cancer compared to healthy controls (OR 0.345, 95% Cl 0.186–0.639, p = 0.001). Besides this, allele frequencies of IL-18 (-137 G/C) and IL-18 (-607 C/A) gene variations in patient with bladder cancer and healthy control groups were significantly different from the Hardy–Weinberg distribution (p

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration. This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method. Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28

Major Histocompatibility Complex Class II (MHCII) is dynamically expressed on intestinal epithelial cells (IECs) throughout the intestine, but its regulation remains poorly understood. We observed that spontaneous upregulation of IEC MHCII in locally-bred Rag1−/− mice correlated with serum Interleukin (IL)-18, was transferrable via cohousing to commercially-bred immunodeficient mice and could be inhibited by both IL-12 and IL-18 blockade. Overproduction of intestinal IL-18 due to an activating Nlrc4 mutation upregulated IEC MHCII via classical inflammasome machinery independently of immunodeficiency or dysbiosis. Immunodeficient dysbiosis increased Il18 transcription, which synergized with NLRC4 inflammasome activity to drive elevations in serum IL-18. This IL-18-MHCII axis was confirmed in several other models of intestinal and systemic inflammation. Elevated IL-18 reliably preceded MHCII upregulation, suggesting an indirect effect on IECs, and mice with IL-18 overproduction showed activation or expansion of type 1 lymphocytes. Interferon Gamma (IFNg) was uniquely able to upregulate IEC MHCII in enteroid cultures and was required for MHCII upregulation in several in vivo systems. Thus, we have linked intestinal dysbiosis, systemic inflammation, and inflammasome activity to IEC MHCII upregulation via an intestinal IL-18-IFNg axis. Understanding this process may be crucial for determining the contribution of IEC MHCII to intestinal homeostasis, host defense, and tolerance., Graphical Abstract

Obesity is frequently associated with cerebrovascular dysfunction; however, the underlying mechanism remains less well understood. In this study, by using pharmacological approaches, we show that neuroinflammation involving microglia plays an important role in obesity-related cerebrovascular dysfunction. PLX3397 treatment, which leads to depletion of microglia, reduced the wall thickness and collagen deposition in the basilar artery of diet-induced obesity (DIO) mice. Besides, the phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 was enhanced, suggesting improved endothelial function of the basilar artery. The wire myography data show that acetylcholine-elicited relaxation of basilar artery isolated from DIO mice was improved after the treatment with PLX3397. Moreover, our data demonstrate that brain administration of IL-18 impaired cerebrovascular function in mice with normal body weight. Together, these data suggest that neuroinflammation involving microglia is important in obesity-related vascular dysfunction in the brain.

This work aims to examine the interaction between apo A2 (Apo A-II) –265T > C SNP and dietary total antioxidant capacity (DTAC) on inflammation and oxidative stress in patients with type 2 diabetes mellitus. The present cross-sectional study included 180 patients (35–65 years) with identified Apo A-II genotype. Dietary intakes were assessed by a FFQ. DTAC was computed using the international databases. IL-18 (IL18), high-sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), serum total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and 8-isoprostaneF2α (PGF2α) markers were obtained according to standard protocols. General linear model was used to evaluate the interaction. The interaction of gene and DTAC (PFRAP = 0·039 and PORAC = 0·042) on PGF2α level was significant after adjusting for confounders. A significant interaction was observed on IL18 level (PORAC = 0·018 and PFRAP = 0·048) and SOD (PTEAC = 0·037) in obese patients. Among patients whose DTAC was higher than the median intake, the levels of hs-CRP and PGF2α were significantly higher only in individuals with CC genotype. Serum TAC (PFRAP = 0·030, PORAC = 0·049) and SOD were significantly lower in the CC genotype. There was a favourable relationship between the high-DTAC and SOD (obese: PTEAC = 0·034, non-obese: PFRAP = 0·001, PTRAP < 0·0001, PTEAC = 0·003 and PORAC = 0·001) and PGF2α (non-obese: PORAC = 0·024) in T-allele carriers. The rs5082 SNP interacts with DTAC to influence several cardiometabolic risk factors. Also, we found dietary recommendations for antioxidant-rich foods intake might be useful in the prevention of diabetes complications in the T carrier more effectively than the CC genotype. Future large studies are required to confirm these results.

Metabolic syndrome (MetS) has become a major clinical challenge worldwide due to rise of urbanisation, surplus energy intake, increasing obesity and sedentary lifestyle. C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-18 (IL-18) are associated with MetS. We performed a systematic review to investigate the effects of exercise on these markers in MetS patients and therefore to determine the best exercise regime for them. We searched Medline (Pubmed and Ovid), Scopus and CINAHL databases. The searches were standardized by using the same search strategy which included the terms such as ‘metabolic syndrome’, ‘CRP’, ‘IL-6’, ‘IL-18’ and ‘exercise’. Only clinical human studies published from Jan 2007 to May 2018 were included. A total of 11 clinical trials (466 participants) were selected. Majority of the studies were randomized controlled studies (90.9%). All studies showed a decrease in serum levels of the biomarkers. However, not all were statistically significant. The main type of exercise in most of the studies was aerobic. Aerobic-resistance exercise was more effective rather than aerobic alone, but aerobic exercise was the only effective as a sole intervention. Aerobic exercise showed promising role as the main lifestyle intervention in MetS. It is concluded that patients with MetS should have combined aerobic-resistance exercise.

Background. Obliterative bronchiolitis (OB) was a main cause of deterioration of long-term prognosis in lung transplant recipients after the first posttransplant year. Proinflammatory cytokine interleukin-18 (IL-18) strengthened both the natural immunity and acquired immunity and played an important role in organ transplantation. The roles of IL-18 in the occurrence, development, and drug treatment of OB remained unclear. Methods. Small interfering RNA (siRNA) against mouse IL-18 (siRNA-IL-18) was used to silence IL-18 expression. Mouse heterotopic tracheal transplantation model was used to simulate OB. Recipient mice were divided into 5 groups ( n = 12 ) according to donor mouse strains and drug treatment: isograft group, allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group. The luminal obliteration rates were pathological evaluation. Expressions of cytokines and MMPs were detected by real-time PCR, western blot, and enzyme chain immunosorbent assay (ELISA). Results. The luminal obliteration rates of IL-18 of the siRNA-IL-18 group were significantly lower than those of the negative control group ( p < 0.0001 ) and the blank control group ( p = 0.0002 ). mRNA expressions of IFN-γ, EMMPRIN, MMP-8, and MMP-9 of the siRNA-IL-18 group were significantly lower than those of the negative and blank control groups. No tracheal occlusion occurred in grafts of the isograft group. The rates of tracheal occlusion of the allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group were 72.17 ± 4.66 %, 40.33 ± 3.00 %, 38.50 ± 2.08 %, and 23.33 ± 3.24 %, respectively. There were significant differences between the 4 groups ( p < 0.001 ). Serum protein expressions of IL-17 ( p = 0.0017 ), IL-18 ( p = 0.0036 ), IFN-γ ( p = 0.0102 ), and MMP-9 ( p = 0.0194 ) were significantly decreased in the allograft+tacrolimus+azithromycin group compared to the allograft group. Conclusions. IL-18 could be a novel molecular involved in the occurrence, development, and drug treatment of OB.

The aim of this study is to investigate the relationship between IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) gene variations and serum trace element levels in patients diagnosed with CRF. Genotype distributions of IL-18 (− 607 C/A, − 137 G/C) gene variations were determined by polymerase chain reaction (PCR) method. PCR-restriction fragment length polymorphism (RFLP) methods were used to determine the MMP-2 (− 1306 C/T) gene variation genotype distributions. Serum trace element levels were determined by atomic absorption spectrophotometer method. A significant difference was found between the CRF patient and healthy control groups in terms of genotype distributions of IL-18 (− 607 C/A) and MMP-2 (− 1306 C/T) gene variations (p

The aim of this study was to investigate the role of IL-18, a member of the IL-1 family, in group B Streptococcus (GBS) infection. Both in a neonatal and adult model of GBS infection, IL-18-deficient animals were significantly more susceptible to infection than WT animals. The lack of IL18 was associated with a marked reduction in IFN-γ-levels after bacterial stimulation but did not play a significant role in the recruitment of PMN to sites of GBS infection. Collectively, our data document a fundamental function of IL-18 signaling in boosting the host immune responses against GBS infection.

This study tested the hypothesis that sickle red blood cell (SS-RBC) can induce inflammasome NLRP3 components gene expression in peripheral blood mononuclear cells (PBMCs) as well as interleukin-1β (IL-1β) and leukotriene B4 (LTB4) production. Additionally, we investigated the effect of hydroxyurea (HU) treatment in these inflammatory markers. PBMCs from healthy donors (AA-PBMC) were challenged with intact and lysed RBCs from SCA patients (SS-RBC) and from healthy volunteers (AA-RBC). NLRP3, IL-1β, IL-18 and Caspase-1 gene expression levels were assessed by quantitative PCR (qPCR). IL-1β protein levels and LTB4 were measured by ELISA. We observed that lysed SS-RBC induced the expression of inflammasome NLRP3 components, but this increase was more prominent for CASP1 and IL18 expression levels. Moreover, we observed that intact SS-RBC induced higher production of IL-1β and LTB4 than lysed SS-RBC. Although SCA patients treated with HU have a reduction in NLRP3 gene expression and LTB4 production, this treatment did not modulate the expression of other inflammasome components or IL-1β production. Thus, our data suggest that caspase-1, IL-1β and IL-18 may contribute to the inflammatory status observed in SCA and that HU treatment may not interfere in this inflammatory pathway.

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine-mediated immune system plays an important role in the pathogenesis of HBV-associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV-associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18, and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR–RFLP. Genotypic distributions between the groups were compared using odd’s ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression levels of pSTAT-1 and pNFƙB was determined by western blotting. In case of IL-18(− 607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(− 137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT-1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV-related disease progression to HCC.

Background Previous studies have shown that polycystic ovary syndrome (PCOS) patients suffer from low-grade chronic inflammation. Furthermore, our previous studies have confirmed that IL-18 is highly expressed in the serum and endometria of PCOS patients. Nevertheless, the mechanisms underlying IL-18 elevation remain unclear. This study aims to explore the signaling pathways that lead to IL-18 upregulation in the endometria of PCOS patients. Methods Using the TF-Search tool, we predicted that C/EBP-β may be a transcription factor for IL-18 and that deacetylase SIRT1 could be involved in its regulation. Subsequently, we analyzed SIRT1 and C/EBP-β in the proliferative endometria of PCOS patients and healthy control using immunohistochemistry, real-time quantitative PCR and western blot; PCOS diagnosis was based on the 2003 Rotterdam ESHRE/ASRM criteria. We further verified the interaction between C/EBP-β and IL-18 using a double luciferase assay. Results SIRT1 and C/EBP-β gene and protein levels in the proliferative endometria of PCOS patients were significantly higher than the control group. Immunohistochemical experiments confirmed that SIRT1 was primarily expressed in the endometrial nucleus, while C/EBP-β was predominantly expressed in the endometrial nucleus and cytoplasm. Double luciferase assay verified the interaction between C/EBP-β and IL-18. Conclusion SIRT1 and C/EBP-β are probable IL-18 regulatory mechanism in the endometria of PCOS patients.

Purpose: To study the effect of traditional Chinese Medicine formula Taoren-Quyu decoction (TQD) on endometriosis. Method: Fifty female Wistar rats were randomly separated into five groups (10 rats/group): normal control, model (untreated) group, positive control (danazol), 200 mg/kg/day (low dose) or 400 mg/kg/day (high dose). All rats were prepared into endometriosis except for normal control rats. TDQ groups rats were orally administered of TQD for 5 weeks. After treatment, the rats were sacrificed by cervical dislocation. The number of total endometriotic lesions were counted. Serum levels of cancer antigen 125 (CA-125), interleukin 13 (IL-13), interleukin 18 (IL-18) and peritoneal fluid tumor necrosis factoralpha (TNF-α) were measured by ELISA kits. Result: Compared with control rats, TQD reduced the number of total endometriotic lesions significantly (12.7 ± 1.2, p < 0.01), as well as serum levels of CA-125 (6.4 ± 1.2 U/mL), IL-18 (118.6 ± 7.4 pg/mL), IL13 (6.3 ± 0.8 pg/mL) and peritoneal fluid TNF-α (231.5 ± 11.7 pg/mL) (p < 0.01). Conclusion: The results reveal that TQD exerts anti-endometriotic effect in rats by inhibiting inflammatory factors. Therefore, TQD has potentials for use in the treatment of endometriosis.

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

It is increasingly reported that a history of concussion may be associated with chronic deleterious consequences. While the pathophysiology that contributes to these consequences is not well understood, neuroinflammation is postulated to be critical. Activation of multi-protein complexes termed inflammasomes, a key component of this inflammatory response, has been reported in more severe TBIs; however, it has not been investigated in milder TBIs, such as concussion. This study investigated serum levels of interleukin (IL)-1β and IL-18 (key proteins activated downstream of these inflammasomes) at acute, sub-acute, and chronic time-points post-concussion. We recruited 105 Australian footballers (65 male, 40 female) during the pre-season, then prospectively followed these players for the occurrence of concussion during the season. At baseline, 58 footballers reported a previous concussion history, and 47 reported no previous concussion history. Additionally, 25 players sustained a mid-season concussion and were sampled at 2, 6, and 13 days post-concussion. Serum levels of IL-1β and IL-18 were quantified using highly sensitive Simoa HD-X Analyzer assays. At baseline, IL-1β levels were higher in male, but not female, footballers with a previous concussion history compared with footballers with no concussion history. There was also a positive correlation between years of collision sport participation and IL-18 levels in males. No evidence was found in males or females to indicate that IL-1β or IL-18 levels differed at 2, 6, or 13 days post-concussion. These findings provide novel insights into potential sex-specific physiological consequences of concussion, and suggest that neuroinflammation may be persistent chronically following concussion in male athletes.

People with HIV (PWH) are at an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Interleukin (IL)-18 is regulated by inflammasomes in response to pathogens and danger signals and has been implicated in both the pathogenesis of NAFLD and HIV disease progression. We hypothesized that increased IL-18 may be associated with NAFLD and liver injury in PWH. This was an observational study of 125 PWH and 59 individuals without HIV in the Boston area. Participants with known hepatitis B, hepatitis C, and excessive alcohol use were excluded. IL-18 was measured in serum by enzyme-linked immunosorbent assay. Liver lipid content was assessed by liver-to-spleen computed tomography (CT) attenuation ratio. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and IL-18 levels were higher in PWH than in controls. In PWH, log(10) IL-18 was associated with log(10)AST (r = 0.34, p = .0001), log(10)ALT (r = 0.33, p = .0002), log(10)HIV RNA (r = 0.29, p = .002), and inversely associated with liver-to-spleen ratio (r = −0.24, p = .02). In addition, log(10) IL-18 was associated with log(10) triglycerides (r = 0.26, p = .003), log(10) MCP-1 (monocyte chemoattractant protein-1; r = 0.33, p = .0004), log(10)caspase-1 (r = 0.35, p

The aim of this study is to establish the content of inflammation markers (tumour necrosis factor alpha and interleukin 18) and the index of total antioxidant activity in young patients with comorbidity between gastroesophageal reflux disease and autoimmune thyroiditis and to determine their dependence on morpho-histological changes in the oesophageal mucosa. Materials and methods. The study involved 182 students aged 18 to 25 years: 120 patients with comorbidity between gastroesophageal reflux disease and autoimmune thyroiditis, 42 those having an isolated course of autoimmune thyroiditis. The methodology included complex clinical, instrumental, immunological, statistical methods. Results. Determining the activity of proinflammatory cytokines has revealed their statistically significant increase. The level of these cytokines depends on morpho-histological changes in the mucous membrane and reaches the maximum during the erosive process. At the same time, the indicator of total antioxidant activity significantly decreases. In this case, the erosive form of the disease is accompanied by more expressive changes in this indicator. Conclusions. The inflammatory process in the oesophagus is accompanied by the activation of the pro-inflammatory segment of immunity against the background of the suppression of the antioxidant system, which is dependent on morphological changes in the oesophageal mucosa. These changes will contribute to the development of pathological apoptosis and the progression of nosologies.

Fish exposed to various threats in the aquatic environment and respond to these with the immune responses which has developed in the evolutionary process. The immune system of teleost fish consists of the fluid and cellular factors of both natural and acquired immunity. Mucosa associated lymphoid tissues are a part of fish immune system and equipped with cells of natural and adaptive immunity. The organs in which all these cells and molecules are formed, matured and included in the system are called lymphoid organs. Cytokines, which are small glycoproteins, play critical roles in immunity. Their main roles in the immune system are to regulate immune responses and to enable communication between cells. In this review, the literature on the main factors of the fish immune system, mucosal immunity, the functions of the primary lymphoid organs, and proinflamatory cytokines IL-1β, TNF-α and IL-18 were collected. Furthermore, the functions of specified cytokines were aimed to clarify.

BackgroundMechanisms underlying the associations of high levels of physical activity (PA) and adherence to the Mediterranean diet (MedDiet) with a better inflammatory profile remain unclear. Our objective was to assess the mediating role of changes in body mass index (BMI) and waist circumference (WC), as markers of body fat in the association of changes in PA and adherence to the MedDiet, with changes in the inflammatory profile.MethodThis study included 489 adults, aged 55–75 years, from the PREDIMED-Plus multicenter lifestyle intervention trial. An inflammatory score was calculated, based on 8 blood biomarkers: high-sensitivity C-reactive protein, interleukin 6, interleukin 8, interleukin 18, monocyte chemo-attractant protein-1, C-peptide, leptin, and regulated on activation, normal T-cell–expressed and secreted chemokine. Biomarkers, levels of PA, score of MedDiet adherence, BMI, and WC were measured at baseline and at 1-year follow-up. Linear regression models were fitted according to the Baron and Kenny framework for mediation analysis.ResultsChanges in BMI and WC mediated the association of both changes in PA and changes in the MedDiet adherence with the inflammatory score. Body mass index mediated 26% of the association of changes in total PA with the inflammatory profile, and 27% of the association of changes in the MedDiet, while WC mediated 13% and 12% of these associations, respectively.ConclusionIn older adults at high cardiovascular risk, increasing PA levels and adherence to a MedDiet during 1 year were associated with a lower inflammatory score, which was partly mediated by a reduction in body fat.Clinical Trials Registration NumberInternational Standard Randomized Controlled Trial Number: ISRCTN89898870; registration date July 24, 2014, retrospectively registered.

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.To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms.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.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).Cohort was small.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.

Objective To identify serum proteins associated with MS and affected by interferon beta treatment. Methods Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a. Results Ten proteins were differentially expressed in MS patients. Five of these were altered by treatment with IFN-β 1a: uPA, CX3CL1, CCL2, TRAIL and IL18. Conclusion CCL2 and TRAIL were confirmed to be modulated with interferon beta treatment in MS. As novel findings, we now report that uPA and CX3CL1 were differentially expressed in MS and increased after IFN-beta-1a treatment. Conflicting results have been reported on how interferon beta affects IL-18. Title in Web of Science: Urokinase, CX3CL1, CCL2, TRAIL and IL-18 induced by interferon-beta treatment

Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis and is a rapidly progressive, life-threatening complication of adult-onset Still disease (AOSD). An an...

Objectives The monoclonal IL-1β antibody canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (SJIA). Its efficacy has been proven in several trials, but not all patients show a complete and sustained response to therapy. We aimed to analyse the association of baseline serum biomarkers with treatment outcome in patients with SJIA treated with canakinumab. Methods Serum samples from 54 patients with active SJIA without recent macrophage activation syndrome (MAS) treated with canakinumab in an open-label response characterization study were subjected to a multiplexed bead array assay. Interesting targets from these analyses were validated by ELISA. Clinical treatment outcomes included modified paediatric ACR (pACR) 30 and 90 responses, clinically inactive disease (CID) within 15 days of treatment and sustained complete response, defined as pACR100 or CID within 15 days of treatment plus no future flare or MAS. Results In canakinumab-naïve patients most biomarkers were elevated when compared with healthy controls at baseline and some rapidly decreased by day 15 [IL-1 receptor antagonist (IL-1RA), IL-6, IL-18 and S100A12]. Responders had higher IL-18 and IFN-γ levels and lower chemokine (C-X-C motif) ligand 9 (CXCL9) levels at baseline, emphasized by the IL-18: CXCL9 and IFN-γ: CXCL9 ratios. These ratios had significant accuracy in predicting treatment responses. Conclusion Differential regulation of the IL-18–IFN-γ–CXCL9 axis is observed in patients with SJIA. Higher IL-18: CXCL9 and IFN-γ: CXCL9 ratios at baseline are associated with a better clinical response to canakinumab treatment in SJIA. Future studies are needed to validate these findings and determine their generalizability to patients with recent MAS.

Inflammatory bowel disease (IBD) is characterized by multiple alterations in cytokine expression and is a risk factor for colon cancer. The Omega class glutathione transferase GSTO1-1 regulates the release of the pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) by deglutathionylating NEK7 in the NLRP3 inflammasome. When treated with azoxymethane and dextran sodium sulphate (AOM/DSS) as a model of IBD, Gsto1−/− mice were highly sensitive to colitis and showed a significant increase in the size and number of colon tumours compared with wild-type (WT) mice. Gsto1−/− mice treated with AOM/DSS had significantly lower serum IL-1β and IL-18 levels as well as significantly decreased interferon (IFN)-γ, decreased pSTAT1 and increased pSTAT3 levels in the distal colon compared with similarly treated WT mice. Histologically, AOM/DSS treated Gsto1−/− mice showed increased active chronic inflammation with macrophage infiltration, epithelial dysplasia and invasive adenocarcinoma compared with AOM/DSS treated WT mice. Thus, this study shows that GSTO1-1 regulates IL-1β and IL-18 activation and protects against colorectal cancer formation in the AOM/DSS model of IBD. The data suggest that while GSTO1-1 is a new target for the regulation of the NLRP3 inflammasome-associated cytokines IL-1β and IL-18 by small molecule inhibitors, there is a possibility that anti-inflammatory drugs targeting these cytokines may potentiate colon cancer in some situations.

Analysis of serum cytokine levels in Wiskott–Aldrich syndrome patients pre‐ and post‐ treatment reveals IL‐18 as a stable and reliable marker of inflammation. Definitive stem cell treatment with good myeloid correction correlates with resolution of inflammation and reduction of circulating IL‐18, highlighting the importance of actin cytoskeletal regulation of myeloid cells in control of inflammation.

Background. Legg–Calve–Perthes disease (LCPD) is an idiopathic avascular femoral head osteonecrosis. The early disease stage is associated with the development of synovitis of the hip joint linked to the overproduction of factors induced by hypoxia as well as of interleukin (IL)-6. Associations of individual polymorphic variants of cytokine genes with LCPD have been shown. Moreover, alterations in the cytokine regulatory cascade are considered an important link in the pathogenesis of synovial inflammation in the early stages of LCPD. Accordingly, this process may be associated with a certain combination of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory cytokines. Aim. This study aimed to study the associations of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory IL with LCPD. Materials and methods. In this case–control study, the main and control groups were composed of 26 children with LCPD and 40 healthy children (all aged 3–11 years), respectively. Genotyping of IL10 (rs1800896), IL13 (rs20541), IL18 (rs187238), IL18 (rs5744292), IL1a (rs1800587 ), IL1RA (POL_GF_58), IL-1Ra (rs4251961), IL1B (rs16944), IL1B (rs1143634), IL4 (POL_GF_59), IL4 (rs2243250), IL6 (rs1800796), IL6 (rs1800795), INF γ (rs2430561), TGF β (rs1800469), and TNF (rs1800629) was performed by polymerase chain reaction (PCR) using TaqMan probes to the corresponding polymorphic variants of genes produced by Thermo Fisher Scientific (USA) on an amplifier ViiATM 7 RealTime PCR System (Life Technologies, USA). Statistical processing of the results was carried out using the SNPstats program and multifactor dimensionality reduction. Results. The study revealed three separate LCPD-potentiating genotypes of polymorphic variants of cytokine genes: IL10 (rs1800896; T>C)*T/C (OR 6.50), IL4 (POL_GF_49, VNTR, Intron4)*2R/2R (OR 12.32), and IL-6 (rs1800796; G>C)*G/C (OR 4.08). Two polymorphic variants of the IL4 gene (POL_GF_49, VNTR, Intron4, and rs2243250; C>T) had a pronounced synergism with respect to the diagnosis of LCPD. Moderate synergy with respect to the diagnosis of LCPD demonstrated the intergenic interaction of IL6 (rs1800796, G>C) with tumor necrosis factor-α (rs1800629, G>A). Moderate antagonism between LCPD and intergenic interactions was obtained for polymorphic variants of IL18 (rs5744292, T>C) and transforming growth factor-β (rs1800469, A>G) genes. Conclusions. The pathogenesis of synovitis and subsequent osteonecrosis in LCPD is associated with a combination of polymorphic variants of the genes of pro-inflammatory and anti-inflammatory cytokines, as well as of DNA variants of the pro-allergic IL4 gene.

OBJECTIVE The aim: Of our research work was to study the level of proinflammatory interleukin-18 (IL-18) in the oral fluid of children with type I diabetes mellitus (DM), and to determine their periodontal status and the level of oral hygiene. PATIENTS AND METHODS Materials and methods: 82 children were examined, they were divided into groups by presence of gingivitis and diabetes mellitus. The level of interleukin-18 in oral fluid was determined by immunoassay. RESULTS Results: In patients with chronic catarrhal gingivitis and type I diabetes mellitus the level of interleukin-18 in oral fluid is the highest (70.91±7.48 pg / ml); the level of interleukin-18 in children with diabetes mellitus and healthy gums is high enough too, it is 14.87±1.11 pg / ml. Interleukin-18 is 3.41±0.25 pg / ml in healthy children with healthy gums. It is 5.74±0.27 pg / ml in somatically healthy children with chronic catarrhal gingivitis. CONCLUSION Conclusions: We indicated that an increase in the value of interleukin-18 in oral fluid is associated with the presence of diabetes mellitus in children. Moreover, this cytokine can be considered as a potential biomarker of gum inflammation in children with diabetes mellitus.

The NLRP3 inflammasome plays a pro-tumorigenic role in various malignancies. However, its potential role in lymphomagenesis remains unclear. In this study, we identified an immunosuppressive state in patients with diffuse large B cell lymphoma (DLBCL), which was characterized by markedly elevated interleukin (IL)-18 levels in lymphoma tissues and positive correlation with programmed death ligand 1 (PD-L1) expression. Furthermore, NLRP3 inflammasome activation in DLBCL cell lines upregulated PD-L1 and reduced the proportion of cytotoxic T cells. NLRP3 inflammasome blockade in vivo suppressed lymphoma growth and ameliorated anti-tumor immunity by downregulating PD-L1 in the tumor microenvironment and decreasing the proportion of PD-1/TIM-3-expressing T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Further in vivo studies revealed IL-18 as the main effector cytokine involved in the negative regulation of anti-lymphoma immunity. Interestingly, NLRP3 blockers combined with anti-PD-L1 treatment exerted antagonistic effects during lymphoma therapy. Altogether, our findings indicate that NLRP3 inflammasome promotes immunosuppression by modulating PD-L1 and immune cells. Accordingly, this study highlights the prognostic and therapeutic values of the NLRP3 inflammasome in lymphoma.

Background: Functional gene polymorphisms of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18) may contribute to the onset and development of Alzheimer’s disease (AD), but the relationships between these polymorphisms and predisposition of AD remain controversial. Objectives: This meta-analysis was conducted to more robustly assess relationships between TNF-α/IL-6/IL-8/IL-18 polymorphisms and predisposition of AD by pooling the findings of relevant studies. Methods: A comprehensive literature searching was performed in PubMed, Embase, Web of Science, Wanfang, and CNKI databases, and 63 studies were found to be eligible for quantitative analyses. Results: The pooled meta-analysis results showed that genotypic frequencies of TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms among AD cases and controls of Asian ethnicity differed significantly. But, we did not observe such genotypic frequencies differences in Caucasians. Conclusions: This meta-analysis suggests that TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms may affect predisposition of AD in Asians, but not in Caucasians.

Background: It is plausible that gene polymorphisms in tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-18 may affect predisposition to microvascular complications of diabetes mellitus (DM), but the results of the so far published studies remain controversial. Objectives: We conducted this meta-analysis to clarify relationships between TNF-α/IL-1/IL-4/IL-8/IL-18 polymorphisms and predisposition to microvascular complications of DM by pooling the findings of eligible studies. Methods: A comprehensive search of PubMed, Embase, Web of Science, and CNKI was endorsed by us to identify already published studies. Forty-nine studies were found to be eligible for the meta-analyses. Results: The pooled meta-analyses results showed that genotypic frequencies of TNF-α −238 G/A, TNF-α −308 G/A, TNF-α −1,031 T/C, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −572 G/C, and IL-18 −137 G/C polymorphisms among patients with diabetic nephropathy (DN) and controls differed significantly. Moreover, genotypic frequencies of TNF-α −238 G/A and IL-8 −251 A/T polymorphisms among patients with diabetic retinopathy (DR) and controls also differed significantly. Conclusions: This meta-analysis suggested that TNF-α −238 G/A, TNF-α −308 G/A, TNF-α −1,031 T/C, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −572 G/C, and IL-18 −137 G/C polymorphisms may affect predisposition of DN. Moreover, TNF-α −238 G/A and IL-8 −251 A/T polymorphisms may affect predisposition of DR.

Juvenile idiopathic arthritis (JIA) represents a group of multifactorial autoinflammatory arthritis diseases. A dysregulated production of pro-inflammatory cytokines is proposed to have a role in the pathogenesis of the disease. Interleukin-18 (IL-18) is one of these pro-inflammatory cytokines. Therefore, this study aimed to define the role of IL-18 in the pathogenesis of JIA. Accordingly, the serum level of IL-18 was determined in 59 Iraqi JIA patients and 58 matched controls. The results revealed a significantly increased median of IL-18 in the patients as compared to the control. A similar increased level was observed in subgroups of patients characterized according to gender, seropositivity for C-reactive protein and rheumatoid factors, juvenile arthritis disease activity score 27 (JADAS27), type of medication, and JIA subtypes. However, JADAS27 showed a significant positive correlation with IL-18 level. Receiver operating characteristic analysis revealed that IL-18 occupied a significant area under the curve, and therefore its significance as a biomarker was suggested. In conclusion, IL-18 is an important biomarker for JIA and may have a role in pathogenesis of disease.

In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), inhibition of the IL1β inflammatory pathway by canakinumab has been shown to significantly reduce lung cancer incidence and mortality. Here we performed molecular characterization of CANTOS patients who developed lung cancer during the study, including circulating tumor DNA (ctDNA) and soluble inflammatory biomarker analysis. Catalogue of Somatic Mutations in Cancer (COSMIC) database ctDNA mutations were detected in 65% (46/71) of the CANTOS patients with lung cancer, with 51% (36/71) having detectable ctDNA at the time point closest to lung cancer diagnosis and 43% (29/67) having detectable ctDNA at trial randomization. Mutations commonly found in lung cancer were observed with no evidence of enrichment in any mutation following canakinumab treatment. Median time to lung cancer diagnosis in patients with (n = 29) versus without (n = 38) detectable COSMIC ctDNA mutations at baseline was 407 days versus 837 days (P = 0.011). For serum inflammatory biomarker analysis, circulating levels of C-reactive protein (CRP), IL6, IL18, IL1 receptor antagonist, TNFα, leptin, adiponectin, fibrinogen, and plasminogen activator inhibitor-1 were determined. Patients with the highest level of baseline CRP or IL6, both downstream of IL1β signaling, trended toward a shorter time to lung cancer diagnosis. Other inflammation markers outside of the IL1β pathway at baseline did not trend with time to lung cancer diagnosis. These results provide further evidence for the importance of IL1β-mediated protumor inflammation in lung cancer and suggest canakinumab's effect may be mediated in part by delaying disease progression of diverse molecular subtypes of lung cancer. Significance: These findings suggest that targeting the IL1β inflammatory pathway might be critical in reducing tumor-promoting inflammation and lung cancer incidence.

Interleukin 18 (IL‐18) is a pleiotropic pro‐inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL‐18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL‐18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL‐18 on folliculogenesis. This work revealed that at 300‐1000 pg/mL, IL‐18 led to a time‐ and dose‐dependently increase in cell proliferation (P

Background: Cytokine polymorphismsmight influence the predisposition to diabetic nephropathy (DN), but the results of already published related studies are still controversial and ambiguous. Objectives: The authors designed this meta-analysis to more precisely estimate relationships between TNF-α/IL-1/IL-4/IL-8/IL-18polymorphisms and DN by pooling the results of already published related studies. Methods: The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. Thirty already published studies were pooled and analyzed in this meta-analysis. Results: The overall pooled meta-analysis results showed that distributions of TNF-α –238 G/A, TNF-α –308 G/A, TNF-α –1031 C/T, IL-1A −889 C/T, IL-1B −511 C/Tand IL-18 –137 G/C polymorphisms among patients and controls differed significantly. Additionally, we also found that distributions of TNF-α –308 G/A, IL-1B −511 C/T and IL-18 –137 G/C polymorphisms among patients and controls from Asians differed significantly, and the distribution of the IL-1B −511 C/T polymorphism among patients and controls from Caucasians also differed significantly. Conclusion: The meta-analysis results demonstrated that TNF-α –238 G/A, TNF-α –308 G/A, TNF-α –1031 C/T, IL-1A −889 C/T, IL-1B −511 C/Tand IL-18 –137 G/Cpolymorphisms might influence predisposition to DN in the overall pooled population. Moreover, TNF-α –308 G/A, IL-1B −511 C/T and IL-18 –137 G/C polymorphisms might influence predisposition to DN in Asians, whereas the IL-1B −511 C/T polymorphism might also influence predisposition to DN in Caucasians.

Objective – to evaluate the relationship between oxidative stress indicators and individual proinflammatory cytokine levels in patients with rosacea.Material and methods. We examined 64 patients with rosacea (49 women, 15 men) aged from 28 to 63 years, of whom 23 were diagnosed with erythematous-telangiectatic and 41 persons with papulopustular rosacea. In patients with rosacea, indicators of oxidative stress were determined -the content of malonic aldehyde in erythrocytes and blood plasma, and fractions of oxidatively modified proteins (OMP Е370, OMP Е430) in blood serum, and the serum content of individual pro-inflammatory cytokines - interleukin-8 (IL-8) and interleukin-18 (IL-18) by enzyme immunoassay. To assess the nature of the relationship between the studied indicators, the methods of correlation analysis were used.Results. In patients with rosacea, there was a significant increase in the content of MA in plasma and erythrocytes compared to the control group (respectively: by 51.4% and 17.3%, p

Summary Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL-18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL-18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL-18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL-18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi-center studies are called for to assess the diagnostic precision of IL-18 for HLH and MAS.

Hyperglycemia causes increased oxidative stress through an imbalance of reactive oxygen species and antioxidative mechanisms. It stimulates the production of inflammatory mediators and cytokines such as TNF-α, interleukin (IL)-1, and IL-18. Goat milk kefir and vitamin D3 have potential as antioxidants and anti-inflammatory agents that can repair damage to pancreatic β cells. This study analyzed the effects of goat milk kefir fortified with vitamin D3 on the IL-18 level in diabetic rats. An experimental randomized pre-post test with control group design was conducted on 20 male Wistar rats divided into four groups, namely negative control (K-), positive control (K+), treatment with unfortified kefir (P1), and treatment with kefir fortified with vitamin D3. The intervention lasted 34 days. Fasting blood glucose and IL-18 levels were measured before and after intervention. Blood glucose and IL-18 levels were analyzed using the glucose oxidase p-aminophenol method and enzyme-linked immunosorbent assay, respectively. No significant increase in the IL-18 level was found in the P1 group with a median of 56.5 (10–252.7) pg/mL to 148.2 (106.8–428.3) pg/mL (p = 0.465) or P2 group with a median of 117.3 (91.8–146.8) pg/mL to 246.7 (168.8–311) pg/mL (p = 0.068), and no significant increase was observed in blood glucose levels in the P1 group (366.9±134.8 mg/dL to 462.1±156.9 mg/dL, p = 0.357) or P2 group (415.0±203.8 mg/dL to 258±129 mg/dL, p = 0.463). Goat milk kefir fortified with vitamin D3 could maintain blood glucose and IL-18 levels.

Background P2Y12 reaction unit (PRU) is an index of platelet activity upon treatment with clopidogrel. In spite of suitable P2Y12 reactions in dual antiplatelet therapy (DAPT) with clopidogrel after percutaneous coronary intervention (PCI), cardiovascular events actually occur in some patients, possibly due to a genetic dysfunction of cytochrome P450 2C19 (CYP2C19), which is a major metabolic enzyme of clopidogrel. As testing the CYP2C19 phenotypes to predict such patients may lack general versatility in daily clinical practice, the aim of this study was to examine whether measuring the blood levels of some cytokines in patients showing desirable PRUs in DAPT with clopidogrel could be a substitute for testing the CYP2C19 phenotypes. Methods We analyzed relationships among PRU, serum levels of 51 cytokines, and CYP2C19 phenotypes in 22 patients receiving DAPT with aspirin and clopidogrel after PCI. Results Seventeen, 18, and 19 of 22 patients indicated PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. Approximately 60% of the patients had a genetically metabolic dysfunction of CYP2C19, and the serum levels of interleukin-18 were independently increased in those patients (p = 0.024 in patients with PRU ≤ 208, p = 0.021 with PRU ≤ 230, and p = 0.020 with PRU ≤ 262). The area under the curves in plot receiver operating characteristics curves for the serum levels of interleukin-18 were 0.94, 0.96, and 0.90 in the non-extensive metabolizer patients with PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. Conclusions The serum levels of interleukin-18 may be a predictor to diagnose patients who receive undesirable DAPT with clopidogrel, possibly due to the genetic dysfunction of CYP2C19 in spite of suitable P2Y12 reactions after PCI.