Interleukins IL-33 and IL-17/IL-17A in patients with ulcerative colitis.
ABSTRACT Disturbance of immune homeostasis in ulcerative colitis (UC) is related to the predominance of T-helper-2 (Th2) immune response. Interleukin (IL)-33 stimulates Th lymphocytes to produce Th2 cytokines, such as IL-4, IL-5, and IL-13, which are believed to induce pathological changes in the intestinal mucosa. The pro-inflammatory role of IL-17 in UC is still unclear. Our aim was to determine serum concentrations of IL-33 and IL-17 in patients with UC and healthy controls.
Serum concentrations of IL-33 and IL-17 were measured in 18 patients (10 men) with UC and 16 control subjects (10 men) by using two-layer immunoenzyme procedure (ELISA).
Median serum concentrations of IL-33 in patients with UC and controls were 140 pg/ mL (interquartile range [IQR], 72.5 pg/mL) and 165 pg/mL (IQR, 140.0 pg/mL), respectively, but the difference was not statistically significant (Mann-Whitney U=112, p = 0.281). The median serum concentration of IL-17/IL-17A in patients with UC was significantly higher (100 pg/mL, IQR 35.75pg/mL) than that in controls (65 pg/ mL, IQR 32.25 pg/mL) (Mann-Whitney U=55, p = 0.002).
Serum concentration of IL-33 in patients with UC was not increased in comparison with that in controls, which is in accordance with current evidence that its primary biological effect is transcriptional rather than cytokinal. Further research is needed to explain whether increased concentration of IL-17 in UC is protective or harmful and to elucidate its immunological and pathogenic role.
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ABSTRACT: Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP), both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro- or anti-inflammatory depending on the disease and the model. In this review the role of IL-33 in the inflammation of several disease pathologies will be discussed, with particular emphasis on recent advances.Journal of Inflammation 08/2011; 8(1):22. · 2.55 Impact Factor
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ABSTRACT: BACKGROUND AND AIMS: Myosin light chain kinase (MLCK) plays a central role in the mechanisms of barrier dysfunction, and intestinal epithelial MLCK protein expression is upregulated in active ulcerative colitis (UC). ML-7, a MLCK inhibitor, has been used in many MLCK studies. However, the effect of ML-7 has never been estimated in colitis models. The aim of this study was to determine whether ML-7 can treat UC. METHODS: Experimental colitis was induced and ML-7 was administered by intraperitoneal injection. The disease activity index (DAI) scores were evaluated and colon tissue was collected for the assessment of histological changes, myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-13 and interleukin (IL)-17 levels. The small intestinal mucosa was ultrastructurally examined, epithelial MLCK protein expression and enzymatic activity were determined, and intestinal permeability was assayed using FITC-dextran 4000 (FD-4) and Evans blue (EB). RESULTS: ML-7 was found to be significantly effective in reducing the DAI scores and histological index scores, and decreasing MPO activity and TNF-α, IFN-γ, IL-13 and IL-17 levels. The small intestinal epithelial MLCK protein expression and enzymatic activity were downregulated by ML-7. The epithelial cells and intercellular tight junctions were ameliorated, and the amount of FD-4 in blood and EB permeating into the intestine were decreased by ML-7 in colitis mice. CONCLUSIONS: ML-7 has a significant anti-colitis effect in colitis mice. It is mainly associated with the inhibition of the epithelial MLCK protein expression, resulting in ameliorated intestinal mucosal permeability.Digestive Diseases and Sciences 07/2012; · 2.26 Impact Factor
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ABSTRACT: IL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis. To evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin. 60 patients with chronic hepatitis C (CHC) and 65 healthy controls were examined and compared for serum IL-33 levels by ELISA. All CHC patients were submitted to liver biopsy either before starting antiviral treatment or during post-treatment follow up. We evaluated whether post-treatment IL-33 concentration was associated with histologic outcome as well as with virologic response to therapy. Serum IL-33 levels were significantly higher among CHC patients in comparison with healthy controls. IL-33 concentration was lower among patients with a METAVIR fibrosis score F1-F2, compared with those having a more advanced liver disease (METAVIR stage F3-F4). In addition, sustained virologic response (SVR) was associated with a significant drop in IL-33 levels, whereas no changes were found among relapsers and nonresponders. Analogously, patients experiencing liver histologic improvement after antiviral therapy had lower post-treatment IL-33 levels in comparison with baseline values. Contrarily, no variations were detected among subjects with worsened or stable histologic features. IL-33 may represent a new and easy-to-detect biomarker for the diagnosis of liver damage in CHC patients, as it appears to be modulated in parallel with biochemical and histologic parameters, such as ALT levels and liver fibrosis. Furthermore, considering that serum IL-33 concentration was significantly reduced following a successful course of antiviral treatment, this cytokine may also represent a sensitive indicator of SVR.Hepatitis Monthly 12/2012; 12(12):e7611. · 1.25 Impact Factor