IL-6 is required for the development of Th1 cell-mediated murine colitis

被引:354
作者
Yamamoto, M
Yoshizaki, K
Kishimoto, T
Ito, H
机构
[1] Osaka Univ, Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Sch Hlth & Sport Sci, Dept Med Sci 1, Suita, Osaka, Japan
关键词
D O I
10.4049/jimmunol.164.9.4878
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn's disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn's disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RB(high) CD4(+) T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-gamma, TNF-alpha and IL-1 beta mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn's disease.
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页码:4878 / 4882
页数:5
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