Essential role for interieukin-6 in the pathogenesis of Crohn's disease

To investigate the role for interleukin-6 (IL-6) signaling in the pathogenesis of Crohn's disease (CD), we introduced anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb) to T-helpher type 1 (Th1) cell-mediated murine colitis and showed complete abrogation of intestinal inflammation by the treatment. Further examination revealed decreased colonic expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1), marked reduction of interferon-gamma, tumor necrosis factor-alpha, IL-1 beta, and inducible nitric oxide synthase mRNA, and increased TUNEL-positive apoptotic cells in the mice treated with anti-IL-6R mAb. These results show that IL-6 signaling plays an important role in the pathogenesis of intestinal inflammation by promoting leukocyte migration and inhibiting apoptosis of T cells; they also suggest a therapeutic potential of anti-IL-6R mAb for human CD.