In:
Journal of Gastroenterology and Hepatology, Wiley, Vol. 18, No. 5 ( 2003-05), p. 578-587
Abstract:
Background and Aims: The imbalance between helper T (Th)1/Th2 cytokines has been observed in human inflammatory bowel disease and various animal models. Because interleukin (IL)‐12 and interferon‐γ (IFN‐γ) productions are known to be a hallmark of Th1‐dominant intestinal inflammation such as 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced colitis, we strictly addressed the roles of IFN‐γ and IL‐12 in the development of colitis, employing knockout mice with IFN‐γ receptor (IFN‐γR) or IL‐12 p40 gene disruptions and mice administered with neutralizing monoclonal antibodies (mAbs) against IFN‐γ or IL‐12. Methods: To induce colitis, 2.5 mg of the hapten reagent TNBS in 50% ethanol was administered into the colon. Two milligrams of rat anti‐mouse IFN‐γ mAb, rat anti‐mouse IL‐12 mAb, or control rat IgG were administered intraperitoneally into mice before TNBS administration. Change in the body weight of mice was evaluated and the degree of inflammation of the colon of these mice was investigated histologically. Immunohistochemical and immunofluorescence analyses were performed to detect CD4 + T cells, macrophages and IL‐12 in TNBS‐induced colitis lesions. The profile of Th1 and Th2 cytokine expressions in colonic tissues was examined by cytokine‐specific semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). Results: Single rectal administration of TNBS developed significant colitis in IFN‐R –/– mice and anti‐IFN‐γ mAb‐pretreated mice, as well as control wild‐type mice. Conversely, administration of TNBS produced no signs of colitis in IL‐12 p40 –/– and anti‐IL‐12 mAb‐pretreated mice. Conclusions: IL‐12, but not IFN‐γ, plays a pivotal role in the pathogenesis of TNBS‐induced colitis. © 2003 Blackwell Publishing Asia Pty Ltd
Type of Medium:
Online Resource
ISSN:
0815-9319
,
1440-1746
DOI:
10.1046/j.1440-1746.2003.03024.x
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
2006782-3
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