title: IL-33 attenuates development and perpetuation of chronic intestinal inflammation.
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-γ), 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.
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Groβ
authors.forename: Kristina
authors.initials: K
authors.lastname: Doser
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Claudia
authors.initials: C
authors.lastname: Hofmann
mesh_terms: D000208:Acute Disease; D000818:Animals; D018988:Bacterial Translocation; D002465:Cell Movement; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000382:microbiology; D008198:Lymph Nodes / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects* / Q000382:microbiology
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D011994:Recombinant Proteins; C554125:interferon gamma-1b; D007371:Interferon-gamma; D016264:Dextran Sulfate; D009195:Peroxidase