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Simple Summary: This research studied how three types of proteins, called interleukins (namely 8, 17A and 33), are present in the blood of healthy people and people with colon cancer. Colon cancer is a disease that affects the large intestine. The paper looked at 82 people, 42 of whom had colon cancer and 40 of whom did not. The researchers divided the cancer patients into four groups based on how severe their cancer was. The study measured the amount of interleukins in the blood of each person using a special test. The paper analyzed the results of the test, considering the age, gender, and cancer stage of each person. The results showed that younger people, and those with less severe cancer had more interleukins in their blood. The paper also found that two of the interleukins (8 and 17A) were higher in the cancer group, while one of them (33) was higher in the healthy group. The study also found that the interleukins were related to each other in both groups. This research concluded that the interleukins might help detect colon cancer and predict how it will progress. This paper could help improve the diagnosis and treatment of colon cancer. This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that circRNAs are involved in the pathogenesis of osteoarthritis (OA) by affecting various fundamental cellular characteristics of chondrocytes. The purpose of this paper is to investigate the role and regulatory mechanism of hsa_circ_0020014 (circ_0020014) in chondrocytes of OA. Methods: The inflammatory cytokine interleukin 1 beta (IL-1β) was used to stimulate human chondrocytes. Cell viability, proliferation, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2′-deoxyuridine (EdU), and flow cytometry assays. Several protein levels were determined by western blotting (WB). Levels of inflammatory cytokines and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). Relative expression of circ_0020014 was estimated by real-time polymerase quantitative chain reaction (RT-qPCR). Bioinformatics prediction combined with dual-luciferase reporter, RIP and RNA pull-down assays were done to probe into the regulatory mechanism of circ_0020014. Results: Circ_0020014 was overexpressed in OA patient-derived articular cartilages and IL-1β-stimulated chondrocytes. Silencing of circ_0020014 lighted IL-1β-prompted chondrocyte proliferation repression, apoptosis, inflammation, and oxidative stress. Mechanically, circ_0020014 functioned as a miR-24-3p molecular sponge to regulate cathepsin B (CTSB) expression. Furthermore, miR-24-3p inhibition alleviated circ_0020014 knockdown-mediation repression of IL-1β-urged chondrocyte injury. In addition, CTSB overexpression whittled miR-24-3p upregulation-mediated suppression of IL-1β-urged chondrocyte injury. Conclusion: Our findings demonstrated that the circ_0020014/miR-24-3p/CTSB axis was associated with IL-1β-prompted chondrocyte injury, supporting the involvement of circ_0020014 in the OA pathogenesis. Highlights: A significant upregulation of circ_0020014 was observed in OA patient-derived articular cartilages. Inhibition of circ_0020014 lessened IL-1β-urged chondrocyte injury. Circ_0020014 could interact with miR-24-3p to mediate CTSB expression. [ABSTRACT FROM AUTHOR]

Psoriasis is a common immune-mediated inflammatory dermatosis affecting 2-3% of the northern European population. Although its aetiology is not completely elucidated, it is widely accepted that activated immune cells and keratinocytes stimulate keratinocyte hyperproliferation by production of cytokines; indeed, elevated amounts of proinflammatory cytokines have been observed in skin lesions and patient serum. By identifying those playing a central role in the disease pathogenesis, it will be possible to indicate a potential therapeutic target. Drugs targeting tumour necrosis factor α (TNF-α), interleukin (IL)-12/23, IL-17, IL-22 and IL-23 and Janus kinase inhibitors have been found to successfully alleviate resistant skin lesions. However, psoriasis is a complex disease with varied cellular interactions and cytokines, and a complex receptor network. Therefore, this review paper examines the less widely known cytokines IL-20 and IL-8, their therapeutic potential and their role in skin lesion development. Although promising results have been obtained for IL-20 and IL-8 treatment, and their role in the psoriasis skin lesion development is well documented, the role of these two cytokines remains overshadowed by that of the wider systemic cytokine storm. [ABSTRACT FROM AUTHOR]

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) cells contain elevated levels of Stat3 and Smad7, two proteins involved in the growth and survival of neoplastic cells. This study was aimed at examining whether Smad7 positively controls the expression of Stat3 in CRC cells. By employing antisense technology, which specifically inhibits Smad7 expression in selected cells, we hereby show that the reduction of Smad7 in CRC cells is paralleled by the marked suppression of the levels of Stat3 and of Stat3-related genes. Finally, we provide evidence that in human CRC tissue samples, there is a positive correlation between Smad7 expression and Stat3 content. Overall, these findings delineate a novel positive feedback loop that sustains CRC cell behavior and suggest that Smad7 is a target for therapeutic intervention in patients with such a disease. Colorectal cancer (CRC) cells contain elevated levels of active signal transducer and the activator of transcription (Stat)-3, which exerts proliferative and anti-apoptotic effects. Various molecules produced in the CRC tissue can activate Stat3, but the mechanisms that amplify such an activation are yet to be determined. In this paper, we assessed whether Smad7, an inhibitor of Transforiming Growth Factor (TGF)-β1 activity, sustains Stat3 expression/activation in CRC cells. Both Smad7 and phosphorylated (p)/activated-Stat3 were more expressed in the tumoral areas of CRC patients, compared to the normal adjacent colonic mucosa of the same patients, and were co-localized in primary CRC cells and CRC cell lines. The knockdown of Smad7 with a Smad7 antisense oligonucleotide (AS) reduced p-Stat3 in both unstimulated and interleukin (IL)-6- and IL-22-stimulated DLD-1 and HCT116 cells. Consistently, reduced levels of BCL-xL and survivin, two downstream signaling targets of Stat3 activation, were seen in Smad7 AS-treated cells. An analysis of the mechanisms underlying Smad7 AS-induced Stat3 inactivation revealed that Smad7 AS reduced Stat3 RNA and protein expression. A chromatin immunoprecipitation assay showed the direct regulatory effect of Smad7 on the Stat3 promoter. RNA-sequencing data from the Tumor, Normal and Metastatic (TNM) plot database showed a positive correlation between Smad7 and Stat3 in 1450 CRC samples. To our knowledge, this is the first evidence supporting the theory that Smad7 positively regulates Stat3 function in CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Bone metastasis in gastric cancer (GC-BM) has received little attention because of its rarity, but the increased pain and shortened survival of patients due to the bone destruction and skeletal-related events (SREs) caused by tumors cannot be ignored. Immune cells and molecules such as RANK-L and GFs in complicated bone microenvironments create suitable conditions for tumor cells to proliferate and break the balance of bone circulation, which leads to osteolysis and osteogenesis. Bone radionuclide scans now are the most sensitive examination for diagnosing bone tumors, and bone-related alkaline phosphatase (ALP) also shows a certain significance in the diagnosis of bone tumors. Combined application of chemotherapeutic drugs, targeted drugs, and immune drugs are the main treatments of GC-BM. This review paper intends to discuss the clinical status of GC-BM, as well as its possible molecular pathogenesis pathways and therapeutic options. Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9–13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer. [ABSTRACT FROM AUTHOR]

Background. Depression is a major cause of disability and most antidepressant medicines are ineffective owing to their high toxicity and numerous adverse effects. As a result, there is an urgent need to find new effective treatment methods. This paper aims to investigate the effect and mechanism of total saikosaponins (TSS) on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Methods. Twenty-four male SD rats were randomly divided into 4 groups: control group, CUMS group, TSS group, and fluoxetine (Flu) group. Then, the following tests were conducted: sucrose preference test, open field test, and elevated plus maze test. Additionally, ELISA was used to detect the levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) in the serum of the rats as well as the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in the hippocampus, and Western blot was used for measuring the expression of brain-derived neurotrophic factor (BDNF) protein and related proteins of the PI3K/AKT/NF-κB signaling pathway in the hippocampus. Results. TSS could significantly improve rat behaviors, specifically indicated by increases in sucrose preference, total movement distance, stay time in the central area, number of entries into open arms, time spent in open arms, and a decrease in stay time in the peripheral area. TSS acted to significantly reduce BDNF protein expression and increase the contents of ACTH and CORT in serum as well as the levels of IL-1β, IL-6, and TNF-α in the hippocampal tissue in rats. In addition, it was able to raise the ratios of p-PI3K/PI3K and p-AKT/AKT and decrease the ratio of p-p65/p65 in tissues, which in turn regulated the PI3K/AKT/NF-κB signaling pathway. Conclusions. TSS, through regulating PI3K/AKT/NF-κB signaling axis, can alleviate depression-like behaviors and elevate neuroendocrine hormone levels and inflammatory factor levels. [ABSTRACT FROM AUTHOR]

The paper is written to investigate the levels and significance of tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), and carbohydrate antigen 19-9 (CA19-9)] and cytokines [interleukin-6 (IL-6), IL-4, and IL-2] in serum and peritoneal lavage fluid of patients with peritoneal metastasis of gastric cancer. For this research, 145 patients with gastric cancer treated in our hospital were divided into peritoneal metastasis group (n = 25), other metastasis group (n = 32), and nonmetastasis group (n = 88) according to the occurrence of metastasis. At the same time, the levels of serum tumor markers and cytokines and tumor markers and cytokines in intraoperative peritoneal lavage fluid were compared among the three groups. The results showed that the proportion of TNM stage III in peritoneal metastasis group and other metastasis group was 68.00% and 62.50%, respectively, and the proportion of tumor >5 cm was 64.00% and 59.38%, respectively, which was significantly higher than that in the control group. The 1-year survival rate of peritoneal metastasis group and other metastasis group was 44.00% and 40.63%, respectively, which was significantly lower than that of nonmetastasis group (P < 0.05).The serum levels of CEA, CA125, CA19-9, IL-6, IL-4, and IL-2 in peritoneal metastasis group and other metastasis group were higher than those in nonmetastasis group. The intraoperative peritoneal lavage fluid CEA, CA125, and IL-6 were 13.41 ± 3.72 ng/ml, 8.97 ± 1.33 U/ml, and 1.85 ± 0.44 pg/ml, respectively, which were higher than those in other metastasis groups and nonmetastasis groups (P < 0.05). There was no significant difference in the levels of CA19-9, IL-4, and IL-2 in peritoneal lavage fluid among peritoneal metastasis group, other metastasis groups, and nonmetastasis groups (P > 0.05); the areas under the ROC curve of intraoperative peritoneal lavage fluid CEA, CA125, and IL-6 in predicting peritoneal metastasis were 0.850, 0.902, and 0.806, respectively, P < 0.05. Thus, the conclusion is that peritoneal lavage fluid CEA, CA125, and IL-6 have certain application value in predicting and diagnosing peritoneal metastasis of gastric cancer, while the other indexes have no application value. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. Objective: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. Methods: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. Results: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). Conclusions: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA. [ABSTRACT FROM AUTHOR]

Background. The flower of Abelmoschus manihot (AM) has been widely used in the treatment of chronic inflammatory diseases, including ulcerative colitis. This paper aimed to confirm the therapeutic effect of AM on ulcerative colitis (UC) and explore its mechanism. Methods. Mouse models were induced by 2.5% dextran sulfate sodium (DSS) and treated with AM. UC signs, symptoms, colon macroscopic lesion scores, and disease activity index (DAI) scores were observed. Colon levels of interleukin- (IL-) 6, IL-1β, IL-18, IL-17, tumor necrosis factor- (TNF-) α, and IL-10 were quantified by ELISA. The colon protein expression levels of NLRP3, ASC, caspase 1 p10, β-arrestin1, ZO-1, occludin-1, and claudin-1 were examined by immunohistochemistry and western blotting. The mRNA levels of IL-1β, IL-18, NLRP3, ASC, and caspase 1 p10 in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). Results. After treatment with AM, the mortality of mice, pathological damage to the colon, splenomegaly, and the spleen coefficient were decreased. AM reduced the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, IL-17, and TNF-α) and increased the level of IL-10. The mRNA expression levels of NLRP3, ASC, and caspase 1 in colon tissue were decreased by AM in a dose-dependent manner. In addition, AM also reduced the protein expression of NLRP3, ASC, caspase 1 p10, IL-1β, IL-18, and β-arrestin1 in the colon tissue of model mice. Western blot analysis confirmed that AM increased the expression of occludin-1, claudin-1, and ZO-1 in a dose-dependent manner. Conclusion. This study shows that AM has a significant therapeutic effect on mice with UC, and the mechanism may be related to the inhibition of the β-arrestin1/NLRP3 inflammasome signaling pathway and the protection of intestinal barrier function. [ABSTRACT FROM AUTHOR]

Objectives The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC). Methods Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774). Results Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P  = 0.0034; I 2 = 71%, Q 2 P  = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P  = 0.045; I 2 = 39%, Q 2 P  = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P  = 0.01; I 2 = 61%, Q 2 P  = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P  < 0.001; I 2 = 10%, Q 2 P  = 0.34) in fibromyalgia patients compared with HC. Conclusion We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia. [ABSTRACT FROM AUTHOR]

The article reports on the research where blood samples of patients suffering from multiple sclerosis are used before their treatment of interferon-β (IFN-β). It states that patients who are benefited from the IFN-β medicine have low levels of a TH17 cytokine, interleukin-17. However, it provides a path to the development of molecular screens for determining multiple sclerosis and also considered as the first hint of a biomarker of what will happen if one does the therapy.

Lung injury was the common and serious complication of sepsis, a systemic inflammatory response syndrome caused by severe infections. Chinese medicine had unique advantages in attenuating inflammatory response, such as Zuojinfang (ZJF). ZJF was a classical compound herb formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6: 1. In this paper, 15 ingredients in ZJF were identified and 8 of them absorbed into rat's serum were quantified by HPLC-MS/MS. Subsequently, sepsis-induced lung injury model was replicated in rats by cecal ligation and puncture. 60 SD rats were randomly divided into 6 groups (n = 10): control group (CON), sham group (Sham), model group (MOD), ZJF low-dose group (ZJF-L), ZJF high-dose group (ZJF-H), and prednisolone group (PNSL). Within the next 24 h, the levels of inflammatory factors, correlation between active ingredients and inflammatory cytokines, the pathological changes of lung tissue, and protein expression of the JAK1/STAT3 signaling pathways were analyzed one by one. Finally, the concentration order of components absorbed in rat serum was berberine > palmatine > jatrorrhizine > coptisine > evodin > chlorogenic acid > evodiamine. Compared with the MOD group, the TNF-α, IL-6, and IFN-γ in the ZJF-H group were significantly reduced (p < 0:05). Moreover, the TNF-α decreased significantly accompanied by the increase of berberine, chlorogenic acid, jatrorrhizine, palmatine, evodin, and evodiamine in serum (negative correlation, p < 0:05). Compared with the MOD, the area of lung injury, the expressions of JAK1, p-JAK1, STAT3, and p-STAT3 were significantly decreased under the treatment of ZJF (p < 0:05). Therefore, downregulating the JAK1/STAT3 signaling pathways was a potential avenue of ZJF in reversing lung injury induced by sepsis. [ABSTRACT FROM AUTHOR]

Caulis Sargentodoxae prescription has been confirmed by the gynecological clinical observation to be effective in the treatment of endometriosis (EMs), and inflammatory cytokines were involved in EMs. In this paper, animal experiments were designed to explain anti-inflammatory mechanisms of Caulis Sargentodoxae prescription on endometriosis. The EMs model was established by autoplastic transplantation, and rats were randomly divided into seven groups: normal control group, model group, ovariectomized group, gestrinone (Western medicine) group, Caulis Sargentodoxae prescription (Chinese medicine) group, celecoxib (inhibitor) group, and combination (Chinese medicine + inhibitor) group. After oral administration for 21 days, the growth inhibitory rates of the ectopic endometria in treatment groups were evaluated, and the levels of inflammatory cytokines in the serum and peritoneal fluid were determined by ELISA, as well as the expression of prostaglandin endoperoxide synthase 2 (PTGS2) in the ectopic endometrial tissues was detected by real-time polymerase chain reaction, immunohistochemistry, and western blotting. The growth inhibitory rates of the ectopic endometria were significantly higher in the Caulis Sargentodoxae prescription group and gestrinone group, in comparison with the model group p < 0.05 . In the Caulis Sargentodoxae prescription group, the levels of inflammatory cytokines including IL-1, IL-2, IL-6, TNF-α, and PGE2 were all reduced in the serum and peritoneal fluid p < 0.05 . In addition, the specific expression of PTGS2 in the ectopic endometrial tissues significantly decreased in the Caulis Sargentodoxae prescription group and PTGS2 inhibitor celecoxib group both at mRNA and protein levels, but in the steroid hormone drug gestrinone group not at the mRNA level. So, Caulis Sargentodoxae prescription has a reliable therapeutic effect on the EMs by its comprehensive anti-inflammatory roles, possibly in a way different from gestrinone. [ABSTRACT FROM AUTHOR]

Trichosanthes tricuspidata Lour., also known as T. palmata Roxb, T. bracteata Lam., T. puber Blume, and Modecca bracteata, is a vine belonging to the Cucurbitaceae family (English name: redball snake gourd). Distributed in China, South and East Asia, and tropical Australia, it has been traditionally used as a medicinal plant for its antifever, laxative, anthelmintic properties and for migraine treatment. In this paper, we examined the effects of Trichosanthes tricuspidata Lour. ethanol extract (Tt-ME) in vitro and in vivo. To confirm the effects of Tt-ME on inflammatory responses, we conducted experimental analyses including level of nitric oxide (NO) production, RT-PCR, and immunoblotting and using a HCl/EtOH-induced gastritis animal model. Tt-ME attenuated the release of NO and decreased mRNA levels of inducible NO synthase (iNOS), TNF-α, and IL-6 in lipopolysaccharide- (LPS-) induced macrophages in a concentration-dependent manner. Tt-ME time-dependently suppressed nuclear translocation of nuclear factor kappa B (NF-κB) subunits p50 and p65, activator protein (AP-1) subunits c-Fos and c-Jun, and STAT3 transcriptional activity by inhibiting nuclear translocation of p50, p65, c-Fos, c-Jun, and STAT3. Tt-ME significantly downregulated NF-κB, MAPK, and JAK2 signaling by targeting Syk, Src, and IRAK1 protein kinases. Furthermore, matrix metalloproteinase-9 (MMP-9) expression and cell migration were observed to be downregulated by Tt-ME in LPS-activated macrophages. In vivo studies on Tt-ME also produced similar trends in Hcl/EtOH-induced gastritis mouse models by inhibiting proinflammatory cytokines and the inflammatory signaling pathway. Our results strongly suggest that Tt-ME exerted anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory disease. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune inflammatory disease characterized by the production of numerous autoantibodies and cytokines, as well as multiple organ damage. Specific B cell subsets negatively regulate immune responses and have been termed regulatory B cells (Bregs). Bregs are characterized by the production of the immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. Bregs suppress other immune cells through the secretion of these immunosuppressive cytokines and have thus been studied extensively for their potential role in the treatment of various autoimmune diseases. The progress of the research on Bregs and SLE in recent years is reviewed in this paper. [ABSTRACT FROM AUTHOR]

It is well accepted that influenza A virus predisposes individuals to often more severe superinfections with Streptococcus pneumonia. However, the mechanisms that lead to this synergy are not clearly understood. Recent data suggests that competent Th17 immunity is crucial to clearance and protection from invasive pneumococcal disease of the lung. We demonstrate that early influenza infection significantly reduced levels of pneumococcus driven IL-12p70, IL-23 and IL-27 in human monocytes with significant impairment of IL-17A and IFN-γ in HKSP-treated allogeneic mixed lymphocyte cultures. We also provide evidence to suggest that the hemagglutinin component of the virus is at least partially responsible for this downward pressure on IL-17 responses but surprisingly this suppression occurs despite robust IL-23 levels in hemagglutinin-treated monocyte cultures. This study demonstrates that influenza can directly affect the immunological pathways that promote appropriate responses to Streptococcus pneumonia in human immune cells. Importance: Influenza virus is highly contagious and poses substantial public health problems due to its strong association with morbidity and mortality. Approximately 250,000–500,000 deaths are caused by seasonal influenza virus annually, and this figure increases during periods of pandemic infections. Most of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial superinfection can result in hospitalisation and/or death of both patients with pre-existing lung disease or previously healthy individuals. The importance of our research is in determining that influenza and its component haemagglutinin has a direct effect on the classic pneumococcus induced pathways to IL-17A in our human ex vivo model. Our understanding of the mechanism which leaves people exposed to influenza infection during superinfection remain unresolved. This paper demonstrates that early infection of monocytes inhibits an arm of immunity crucial to bacterial clearance. Understanding this mechanism may provide alternative interventions in the case of superinfection with antimicrobial resistant strains of bacteria. [ABSTRACT FROM AUTHOR]

Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase (DPP-4). It increases the levels of the active form of incretins such as GLP-1 (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their means positively affects glucose metabolism. It is successfully applied in the treatment of diabetes mellitus type 2. The most recent scientific reports suggest beneficial effect of sitagliptin on diseases in which neuron damage occurs. Result of experimental studies may indicate a reducing influence of sitagliptin on inflammatory response within encephalon area. Sitagliptin decreased the levels of proinflammatory factors: TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation 163), and contributed to an increase in levels of anti-inflammatory factors: IL-10 (interleukin-10) and TGF-β (transforming growth factor β). Moreover, sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying glutamate and glutathione levels within the region of hippocampus in mice. It has been observed that sitagliptin decreases accumulation of β-amyloid within encephalon structures in experimental models of Alzheimer’s dementia. This effect may be connected with SDF-1α (stromal cell-derived factor 1α) concentration. Administration of sitagliptin caused a significant improvement in MMSE (Mini–Mental State Examination) tests used for assessment of dementias. The paper presents potential mechanisms of sitagliptin activity in conditions connected with neuroinflammation with special emphasis on Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Caulophyllum robustum Maxim (C. robustum) has commonly been used as traditional Chinese medicine for the treatment of rheumatic pain and rheumatoid arthritis (RA) in China. This paper first investigated the anti-inflammation effect of C. robustum extraction (CRME) on RAW264.7 cells stimulated by lipopolysaccharide (LPS) and gene expression levels of inflammatory factors. Moreover, we first evaluated the anti-RA effects of CRME using collagen-induced arthritis (CIA) in DBA/1J mice, and the incidence, clinical score, and joint histopathology were evaluated. The levels of IL-1, IL-6, TNF-α, and PGE2 inflammatory factors in sera of mice were detected by enzyme-linked immunosorbent assay. The expression of NF-κB p65 in the joint was tested by immune histochemical technique. The results showed that, compared with the model group, CRME significantly improved symptoms of the arthritis index, limb swelling, and histological findings by decreasing synovial membrane damage, the extent of inflammatory cell infiltration, and the expansion of capillaries in CIA mice. The results also showed that CRME can reduce the levels of IL-1, IL-6, TNF-α, and PGE2 and inhibit the expression of NF-κB p65. All these results indicated the anti-inflammatory efficacy of CRME as a novel botanical extraction for the treatment of RA. [ABSTRACT FROM AUTHOR]

Osteoporosis and periodontal disease (PD) are two chronic diseases, characterized by bone loss, with systemic or local impact (alveolar bone). Both pathologies have a progressive evolution, leading to systemic bone loss in the case of osteoporosis and bone lysis localized in the alveolar bone in the case of periodontal disease. The present paper presents recent data from the literature on the association between periodontal disease and osteoporosis, on the role of cytokines in the bone resorption-apposition imbalance, and on how periodontal disease causes changes in serum levels of cytokines, leading to disorders in the systemic bone formation. We also found it useful, especially for rheumatologists, to outline the extent to which periodontal disease can create a systemic context favorable to the development of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Acne is a dermatosis characterized by a chronic folliculitus caused by Propionibacterium acnes associated to keratinization disturbance of corneal layer with comedons formation and fat overproduction named seborrhea. Is a skin illness that affects pilosebaceous follicles. Provokes inflammatory and non inflammatory lesions in skin zones with more sebaceous glands as face, chest ant the upper back. Affects approximately 80% of humans between 11 and 30 years old. Objective: To quantify the production of IL-1β, IL-8 and TNF-α directly to inflammatory acne lesions that showed delayed hypersensitivity response in patients by ELISA technique. Patients and methods: To 40 patients from Centro Dermatologico Ladislao de la Pascua with inflammatory acne was cleaned at the sample zone and by punction with a sterile lancet. The sample was recovered in a filter paper directly. Before to develop the ELISA technique the paper filter was impregned with 300 µL of sterile saline solution. The cytokines were quantified by commercial kits Quantikine R&D systems IL-1β (DBL 50), IL-8 (D800c) and TNF-α (DTA00C). Results: 26 of 40 patients showed at least one of the interleukins elevated and represent 65% of population. The rest of patients (14) had normal values (35%). The cytokine that showed the highest concentration in the majority of patients was IL-8 (16), IL-1β (13) and TNF-α (11) respectively. Discussion: Our results demonstrate clearly that 65% of the patients have high concentrations al least of one interleukin derived from inflammatory cells that were attracted and activated by inflammatory process induced by P. acnes in skin. Those patients with treatment compared against control patients without treatment present similar values in IL-8 and TNF-α; however, the IL-8 was present in high concentration in larger patients (40%), TNF-α in 27% and IL-1β was reduced in patients with treatment (5%) comparatively to patients without treatment (27%). With these results we think that anti-inflammatory drugs used in these treatments inhibit the production of IL-1β that is an important molecule in inflammatory response. Conclusion: In 65% of the patients with inflammatory acne it was demonstrated that cells present in lesions were activated because the levels of cytokines IL-8, IL-1β y TNF-α are elevated in this order in these samples. [ABSTRACT FROM AUTHOR]

The article presents information about abstracts of various papers that will be discussed at the Discussion Group of the 6th European Congress on Epileptology that will be held on June 1, 2004. One of the papers that will be discussed is "Cytokines and Acute Neurodegeneration in CNS Disorders," by S. Allan. Cytokines are a large and varied group of immune molecules that have diverse actions in the brain, including a key role as mediators of acute neurodegeneration. Other papers that will be discussed are "The Role of the Interleukins in Febrile Seizures," by R. Straussberg and "The Significance of Cytokine Production in Clinical Epilepsy," by J. Peltola and K.A. Lehtimaki.

Enhancement or inhibition of cytokine signaling and corresponding immune cells responses are critical factors in various disease treatments. Cytokine signaling may be inhibited by cytokine-neutralizing antibodies (CNAs), which prevents further activation of cytokine receptors. However, CNAs may result in enhanced—instead of inhibitory—cytokine signaling (an “agonistic effect”) in various in vitro and in vivo experiments. This may lead to lack of efficacy or adverse events for cytokine-inhibiting based medicines. Alternatively, cytokine-antibody complexes may produce stronger signaling vs. cytokine alone, thereby increasing the efficacy of stimulating cytokine-based drugs, at equal or lower cytokine doses. In this paper, the effect of cytokine signaling enhancement by a CNA was studied in a generic mathematical model of interleukin-4 (IL-4) driven T-cell proliferation. The occurrence of the agonistic effect depends upon the antibody-to-cytokine binding affinity and initial concentrations of antibody and cytokine. Model predictions were in agreement with experimental studies. When the cytokine receptor consists of multiple subunits with substantially differing affinities (e.g., IL-4 case), the choice of the receptor chain to be blocked by the antibody is critical, for the agonistic effect to appear. We propose a generic mechanism for the effect: initially, binding of the CNA to the cytokine reduces free cytokine concentration; yet, cytokine molecules bound within the cytokine-CNA complex—and released later and over time—are “rescued” from earlier clearance via cellular internalization. Hence, although free cytokine-dependent signalling may be less potent initially, it will also be more sustained over time; and given non-linear dynamics, it will lead ultimately to larger cellular effector responses, vs. the same amount of free cytokine in the absence of CNA. We suggest that the proposed mechanism is a generic property of {cytokine, CNA, receptor} triads, both in vitro and in vivo, and can occur in a predictable fashion for a variety of cytokines of the immune system. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most prevalent cause of liver disease worldwide and afflicts adults and children as currently associated with obesity and insulin resistance. Even though lately some advances have been made to elucidate the mechanism and causes of the disease much remains unknown about NAFLD. The aim of this paper is to discuss the present knowledge regarding the pathogenesis of the disease aiming at the initial steps of NAFLD development, when inflammation impinges on fat liver deposition. At this stage, the Kupffer cells attain a prominent role. This knowledge becomes subsequently relevant for the development of future diagnostic, prevention, and therapeutic options for the management of NAFLD. [ABSTRACT FROM AUTHOR]

In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-lβ -31 T/C, IL-6 -174 G/C, tumor necrosis factor a (TNF-α) -308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5' nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-lβ -31C, IL-6 -174G, TNF-α -308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age⩽40years (aOR=3.7, 95%CI=1.5–8.9, P =0.004), low activity of gamma glutamyl transferase (GGT) (aOR=0.9, 95%CI=0.98–0.99, P =0.028), CC genotype of IL28B polymorphim (aOR=2.7, 95%CI=1.0–7.2, P =0.044) and low IL-6 (aOR=0.5, 95%CI=0.3–1.0, P =0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P =0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P ⩽0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P =0.003 and P ⩽0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR. Conclusions: CC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment. [Copyright &y& Elsevier]

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis and included in seronegative spondy-loarthropathy. PsA has several unique characteristics different from rheumatoid arthritis (RA), such as enthesopathy, dactylitis, and abnormal bone remodeling. As compared with synovitis of RA (pannus), proliferation of PsA synovium is mild and characterized by hypervascularity and increased infiltration of polymorphonuclear leukocytes in the synovial tissues. Angiogenesis plays a crucial role in cutaneous psoriasis, and several angiogenic factors such as vascular endothelial growth factor, interleukin-8, angiopoietin, tumor necrosis factor-α and transforming growth factor-β, are suggested to play an important role also in the pathophysiology of PsA. Further, IL-17 has various functions such as upregulation of proinflammatory cytokines, attraction of neutrophils, stimulation of keratinocytes, endothelial cell migration, and osteoclast formation via RANKL from activated synovial fibroblasts.Thus, IL-17 may be important in angiogenesis, fibrogenesis, and osteoclastogenesis in PsA. In this paper, roles of angiogenesis in the psoriatic synovium are discussed, which may strengthen the understanding of the pathogenesis of PsA. [ABSTRACT FROM AUTHOR]

Behçet disease is a chronic relapsing vasculitis with unclear etiology and immunopathogenesis. Antigenic stimuli, antigen presenting cells, T cells, monocyte, and neutrophil and endothelial cells are major parts of the pathology of the disease. Understanding of the new pathogenic mechanisms based on molecular structure of the disease helps us in improving the novel therapeutic modalities. These drugs target specific and nonspecific inhibition of the immun system. These therapies include biologic agents, new topical and systemic immunosuppressants, tolerizing agents, and immunoablation. Novel treatment will be promising to treat the especially recalcitrant cases to conventional therapy. In this paper, new aspect of the immunopathogenesis of Behçet's diseases and novel treatment modalities will be discussed. [ABSTRACT FROM AUTHOR]

Substantial advances have been made in understanding the biology of multiple myeloma (MM) through the study of the bone marrow (BM) microenvironment. Indeed, the BM niche appears to play an important role in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM niche is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a noncellular compartment including the extracellular matrix (ECM) and the liquid milieu (cytokines, growth factors, and chemokines). In this paper we discuss how the interaction between the malignant plasma cell and the BM microenvironment allowed myeloma progression through cell homing and the new concept of premetastatic niche. [ABSTRACT FROM AUTHOR]

Metabolic dysregulation, including abnormal glucose utilization and insulin resistance or deficiency, occurs at an early stage of AD independent of type II diabetes mellitus (T2DM). Thus, AD has been considered as type 3 diabetes. T2DM is a risk factor for AD; the coexistence of these two diseases in a society with an increasing mean age is a significant issue. Recently, research has focused on shared molecularmechanisms in these two diseases with the goal of determining whether treating T2DM can lessen the severity of AD. The progress in this field lends strong support to several mechanisms that could affect these two diseases, including insulin resistance and signaling, vascular injuries, inflammation, and the receptor for advanced glycation endproducts and their ligands. In this paper, we focus on inflammation-based mechanisms in both diseases and discuss potential synergism in these mechanisms when these two diseases coexist in the same patient. [ABSTRACT FROM AUTHOR]

T cell lines with defined cytokine profiles are an invaluable tool for assessing the control of immune responses both in vitro and in vivo. Production of such cell lines can be complex and time-consuming. Here we present a powerful technique to assay the cytokines produced by T cells activated polyclonally or with specific antigens. This paper presents a detailed methodology for the identification and isolation of cytokine-producing T cells activated with the artificial superantigen, CytoStim, or viral and fungal antigens. These cells can be analysed for different cytokines simultaneously, or cultured further to rapidly establish T cell lines making known cytokine types. We highlight the enumeration, isolation and phenotype of interleukin-17-producing T cells, and the rapid generation of virus-specific Th1 T cell lines. [ABSTRACT FROM AUTHOR]

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Are T helper 17 cells really pathogenic in autoimmunity? Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04039.x CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04040.x Development of mouse and human T helper 17 cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04041.x Uncommitted (naive) CD4+ T helper cells (Thp) can be induced to differentiate to specific lineages according to the local cytokine milieu, towards T helper type 1 (Th1), Th2, Th17 and regulatory T cell (Treg) phenotypes in a mutually exclusive manner. Each phenotype is characterized by unique signalling pathways and expression of specific transcription factors, notably T-bet for Th1, GATA-3 for Th2, forkhead box P3 (FoxP3) for Tregs and receptor-related orphan receptor (ROR)α and RORγt for Th17 cells. Tregs and Th17 cells have been demonstrated to arise from common precursors in a reciprocal manner based on exposure to transforming growth factor (TGF)-β or TGF-β plus interleukin (IL)-6 and carry out diametrically opposing functions, namely suppression or propagation of inflammation, respectively. However, while epigenetic modifications in Th1 and Th2 differentiated cells prevents their conversion to other phenotypes, Th17 cells generated in vitro using TGF-β and IL-6 are unstable and can convert to other phenotypes, especially Th1, both in vitro and in vivo. Tregs are generated from naive precursors both in the thymus (natural, nTregs) and in the periphery (induced, iTregs). The highly suppressive function of Tregs enables them to control many inflammatory diseases in animals and makes them particularly attractive candidates for immunotherapy in humans. The stability of the Treg phenotype is therefore of paramount importance in this context. Recent descriptions of Treg biology have suggested that components of pathogens or inflammatory mediators may subvert the suppressive function of Tregs in order to allow propagation of adequate immune responses. Unexpectedly, however, a number of groups have now described conversion of Tregs to the Th17 phenotype induced by appropriate inflammatory stimuli. These observations are particularly relevant in the context of cell therapy but may also explain some of the dysregulation seen in autoimmune diseases. In this paper, we review Treg to Th17 conversion and propose some potential mechanisms for this phenomenon. [ABSTRACT FROM AUTHOR]

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Induction of interleukin-17 production by regulatory T cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04038.x Are T helper 17 cells really pathogenic in autoimmunity? Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04039.x CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04040.x There has been a considerable amount of interest in the immunological community about new phenotypic subsets of CD4+ T cells, particularly cells that produce the cytokine interleukin (IL)-17 [named T helper type 17 (Th17) cells]. While the initial discovery of Th17 cells and the pathways that controlled their development was in the mouse, recent attention has shifted to the existence of these cells and the relevant upstream cytokine signals in humans. While it is clear that CD4+ T cells producing IL-17 exist in vivo, their relevance to disease pathogenesis is only just being understood. In this paper, we review the data regarding the generation of human Th17 cells in vitro and the evidence that this effector population is important in human disease states. [ABSTRACT FROM AUTHOR]

Alopecia areata, a disease of the hair follicles with multifactorial etiology and a strong component of autoimmune origin, has been extensively studied as far as the role of several cytokines is concerned. So far, IFN-γ, interleukins, TNF-α, are cytokines that are well known to play a major role in the pathogenesis of the disease, while several studies have shown that many more pathways exist. Among them, MIG, IP-10, BAFF, HLA antigens, MIG, as well as stress hormones are implicated in disease onset and activity. Within the scope of this paper, the authors attempt to shed light upon the complexity of alopecia areata underlying mechanisms and indicate pathways that may suggest future treatments. [ABSTRACT FROM AUTHOR]

Human interleukin-7 (hIL-7) is a cytokine secreted by the stromal cells of the red marrow. It is important for proliferation during certain stages of B-cell maturation and for T and NK cell survival, development, and homeostasis. It is a critical growth factor for enhancement and recovery of the immune T-cell. Because of its strong immunomodulatory effects, hIL-7 may become a valuable supplementary agent for immunotherapeutical treatments in patients with HIV infection or immunodeficiency. Human IL-7 has previously been produced in various protein expression systems. In this paper, we present an alternative expression system, in Spodoptera frugiperda cells, for the production of hIL-7 using nonlytic vector systems. This system allows generation of correctly translated and accurately processed heterologous proteins as soluble recombinant proteins. Here we report plasmid construction, transfection, and consequent expression of hIL-7 using this nonlytic insect cell expression system. The levels of secreted hIL-7 in a small scale experiment reached a level of 1.7 μg·1-1 under serum-free cell culture conditions. [ABSTRACT FROM AUTHOR]

Dietary fish oil has immunomodulatory effects that are partly mediated by its effects on cytokine secretion. In this paper, we examine whether dietary fish oil has different effects on cytokine secretion by T cells and macrophages. Female BalbC mice were fed diets supplemented with 18% fish oil + 2% corn oil or 20% corn oil. Concanavalin A (ConA)- and LPS-induced TNF-alpha and IL-10 secretion by splenocytes was examined using ELISA. Dietary fish oil decreased ConA induced-, but increased LPS-induced, TNF-alpha and IL-10 secretion by total murine splenocytes. Dietary fish oil increased the number of splenocytes secreting TNF-alpha and IL-10, following stimulation with LPS, by 123 and 38%, respectively, but did not affect cytokine secretion by each cell, as determined using enzyme-linked immunospot. Spleens from mice fed the fish oil diet had over 2-fold higher proportion of macrophages with high expression of CD11b than spleens from mice fed the corn oil diet. In addition, fish oil increased the proportion of total and CD11b(+) splenocytes that expressed the LPS receptor complex molecules, CD14 and toll-like receptor (TLR)4/myeloid differentiation factor-2 (MD-2), by 85 and 28%, respectively. The increased proportion of macrophages expressing the LPS receptor complex molecules, CD14 and TLR4/MD-2, in spleens from mice fed the fish oil diet may explain the increased number of cells that secreted the cytokines after LPS stimulation. [ABSTRACT FROM AUTHOR]

The aim of this paper is to determine the involvement of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 in intermediate CRPS 1 as locally formed mediators of inflammation. In this study, 25 patients with proven CRPS 1 (Bruehl criteria) were included. All patients participated in one of our earlier studies during the acute stage of their disease. After the disease developed into an intermediate stage, both the disease activity and the profile of inflammatory mediators were reevaluated. Disease activity and impairment were determined by means of a visual analogue scale, the McGill Pain Questionnaire, the difference in volume and temperature between the involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Suction blisters were made on the involved and uninvolved extremities for measurement of IL-6 and TNF-α. A significant improvement in signs and symptoms of impairment was found. However, the levels of IL-6 and TNF-α in blister fluid in the involved extremity versus uninvolved extremity were still significantly raised. Although signs and symptoms are significantly improved, proinflammatory cytokines are still increased in CRPS 1 affected extremities during the intermediate stage of the disease. This indicates that the initiation and sustained development of the disease are only partially affected by proinflammatory cytokines. Follow-up in the chronic stage is necessary to draw more definite conclusions about the existence of a supposed relation between clinical signs and symptoms and the level of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Interleukin 18 (IL-18) has been identified as a potent upstream cytokine required for upregulation of IFN-γ secretion that plays a crucial role in polarization of Th1 type of immune response. Considering the potential applications of the cytokine in immunomodulation, it has been characterized in many livestock species including cattle, equines, canines, felines and porcines. In this paper we report the isolation, cloning sequencing and expression of caprine precursor IL-18. Full-length caprine IL-18 cDNA was isolated from mitogen-stimulated adherent peripheral blood mononuclear cells using reverse transcription polymerase chain reaction (RT-PCR). The cDNA contained an open reading frame of 579 bp encoding a putative polypeptide of 192 amino acids. Deduced amino acid sequence of caprine IL-18 showed varying amino acid identity with the published sequences of other domestic ruminant species ranging from 94.3% to 96.9%, while it shared over 78% aa identity with other domestic animals. Pairwise multiple aligned sequences showed a deletion of Glu31in caprine IL-18 unlike in other species. Recombinant caprine IL-18 was produced in Escherichia coli, which cross-reacted with two antiporcine IL-18 monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Lipoarabinomannans (LAMs) are major lipoglycans of the mycobacterial envelope and constitute immunodominant epitopes of mycobacteria. In this paper, we show that mannose-capped (ManLAM) and non-mannose- capped (PILAM) mycobacterial lipoglycans insert into T helper cell rafts without apparent binding to known receptors. T helper cells modified by the insertion of PILAM responded to CD3 cross-linking by decreasing type 1 (IL-2 and IFN-?) and increasing type 2 (IL-4 and IL-5) cytokine production. Modification by the mannose-capped ManLAMs had similar, but more limited effects on T helper cell cytokine production. When incorporated into isolated rafts, PILAMs modulated membrane-associated kinases in a dose-dependent manner, inducing increased phosphorylation of Src kinases and Cbp/PAG in Th1 rafts, while decreasing phosphorylation of the same proteins in Th2 rafts. Mycobacterial lipoglycans thus modify the signalling machineries of rafts/microdomains in T helper cells, a modification of the membrane organization that eventually leads to an overall enhancement of type 2 and inhibition of type 1 cytokine production. [ABSTRACT FROM AUTHOR]

Inflammatory response represents one of the main mechanisms of healing and tissue function restoration. On the other hand, chronic inflammation leads to excessive secretion of pro-inflammatory cytokines involved in the onset of several diseases. Oxidative stress condition may contribute in worsening inflammatory state fall, increasing reactive oxygen species (ROS) production and cytokines release. Polyphenols can counteract inflammation and oxidative stress, modulating the release of toxic molecules and interacting with physiological defenses, such as cytochromes p450 enzymes. In this paper, we aimed at evaluating the anti-inflammatory properties of different concentrations of Myrtus communis L. pulp and seeds extracts, derived from liquor industrial production, on human fibroblasts. We determined ROS production after oxidative stress induction by H2O2 treatment, and the gene expression of different proinflammatory cytokines. We also analyzed the expression of CYP3A4 and CYP27B1 genes, in order to evaluate the capability of Myrtus polyphenols to influence the metabolic regulation of other molecules, including drugs, ROS, and vitamin D. Our results showed that Myrtus extracts exert a synergic effect with vitamin D in reducing inflammation and ROS production, protecting cells from oxidative stress damages. Moreover, the extracts modulate CYPs expression, preventing chronic inflammation and suggesting their use in development of new therapeutic formulations. [ABSTRACT FROM AUTHOR]