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

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn's disease. Among those cytokines, strong expressi on of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 i n the pathogenesis of Crohn's disease, we introduced anti-IL-6R mAb to a mu rine 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 Ig G was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expressi on were analyzed by immunohistochemistry. Colonic cytokine expression was d etermined by RT-PCR. Mice treated with mAb showed normal growth, whereas co ntrols 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 remarkabl e 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 t he pathogenesis of murine colitis and suggest a therapeutic potential of an ti-IL-6R mAb for treatment of human Crohn's disease.