IL-33 attenuates development and perpetuation of chronic intestinal inflammation

Gross, Philipp and Doser, Kristina and Falk, Werner and Obermeier, Florian and Hofmann, Claudia (2012) IL-33 attenuates development and perpetuation of chronic intestinal inflammation. INFLAMMATORY BOWEL DISEASES, 18 (10). pp. 1900-1909. ISSN 1078-0998, 1536-4844

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Abstract

Background: Interleukin-33 (IL-33) is a member of the IL-1 family. Recent evidence shows the importance of IL-33 in autoimmune and inflammatory diseases. To elucidate its impact on inflammatory bowel disease we studied the effects of exogenous IL-33 during the induction of acute dextran sodium sulfate (DSS)-induced colitis, the induction period of chronic DSS colitis, and after establishment of chronic inflammation. Methods: For induction of acute colitis mice received DSS in their drinking water for 7 days and were killed at day 8 or 14 after first DSS administration. Chronic colitis was induced by four cycles of DSS. Animals were treated with IL-33 between the DSS cycles (intermediate treatment) or after onset of chronic disease (posttreatment). Colons and mesenteric lymph nodes were isolated for histology and cytokine secretion, flow cytometric analysis, determination of myeloperoxidase, and transcription factor activity. Results: While IL-33 in acute colitis led to slight aggravation of inflammation, both chronic colitis approaches resulted in a significant reduction of inflammatory colon contraction, amelioration of disease scores, suppression of interferon-gamma (IFN-?), and a shift to T helper (Th)2-associated cytokines. Examination of colon tissue revealed increased Ly6g-mRNA levels and myeloperoxidase (MPO) activity in IL-33-treated animals. Evaluation of bacterial translocation revealed decreased translocation incidence in IL-33-treated mice. Conclusions: In summary, IL-33 has extenuating effects in chronic DSS-induced colitis: Excessive Th1-directed cytokine responses are shifted toward Th2-like immune reactions and general inflammation parameters are reduced. IL-33-induced neutrophil influx during chronic inflammation reduced translocation of pathogenic bacteria across damaged epithelium. (Inflamm Bowel Dis 2012)

Item Type: Article
Uncontrolled Keywords: BOWEL-DISEASE; ULCERATIVE-COLITIS; T-CELLS; IN-VIVO; INDUCED ARTHRITIS; ST2 RECEPTOR; MAST-CELLS; CYTOKINE; MICE; PATHOGENESIS; IL-33; intestinal immune system; chronic DSS-colitis; chronic experimental colitis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 May 2020 04:52
Last Modified: 06 May 2020 04:52
URI: https://pred.uni-regensburg.de/id/eprint/18064

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