Anti-IL-6 receptor monoclonal antibody inhibits leukocyte recruitment and promotes T-cell apoptosis in a murine model of Crohn's disease.

Autor: Ito, Hiroaki, Hirotani, Tomonori, Yamamoto, Mitsunari, Ogawa, Hiroyuki, Kishimoto, Tadamitsu
Předmět:
Zdroj: Journal of Gastroenterology; 2002 Supplement 14, Vol. 37 Issue 11, p56, 6p
Abstrakt: Background. To assess the contribution of IL-6 signaling to the physiopathology of Crohn's disease, we introduced anti-IL-6 receptor monoclonal antibody to a murine colitis model. Methods. Colitis was induced in C.B-17-scid mice to which were transferred CD45RB[sup high] CD4[sup +] T cells from Balb/c mice. Anti-IL-6 receptor monoclonal antibody or rat IgG was given intraperitoneally after T-cell transfer, followed by weekly injection. Vascular adhesion molecules and inducible nitric oxide synthase were visualized by immunostaining. Cytokine expression was determined by RT-PCR, and apoptotic cells were determined by the TUNEL method. Results. Mice treated with anti-IL-6 receptor monoclonal antibody showed normal growth while controls lost weight. Colitis was improved histologically with reduced infiltration of LFA-1[sup +] monocytes/ macrophages and VLA-4[sup +] T cells. ICAM-1 and VCAM-1 expression in the colonic vascular endothelium was markedly suppressed by the treatment, whereas no significant difference was seen in MAdCAM-1. IFN-γ, TNF-α, and IL-1β mRNAs were markedly reduced, but no difference was observed in the expression of IL-4, IL-10, and TGF-β. Inducible nitric oxide synthase was upregulated in the mucosa of colitic mice and downregulated in the treated mice. Apoptotic cells were very sparse despite massive CD4[sup +] T-cell infiltration in colitic mice, whereas increased apoptosis was seen in the treated mice with an apparently reduced number of T cells. Conclusions. AntiIL-6 receptor monoclonal antibody abrogated murine colitis. It effectively blocked the expression of adhesion molecules, thereby blocking leukocyte recruitment, and increased T-cell apoptosis. These results strongly suggest the therapeutic potential of anti-IL-6 receptor monoclonal antibody for human Crohn's disease. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz: