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Journal of Gastroenterology

, Volume 37, Supplement 14, pp 56–61 | Cite as

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

  • Hiroaki Ito
  • Tomonori Hirotani
  • Mitsunari Yamamoto
  • Hiroyuki Ogawa
  • Tadamitsu Kishimoto
Biotherapy and biological response modifiers for IBD

Abstract

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 CD45RBhigh CD4+ 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+ monocytes/ macrophages and VLA-4+ 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-lβ 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+ T-cell infiltration in colitic mice, whereas increased apoptosis was seen in the treated mice with an apparently reduced number of T cells. Conclusions. Anti-IL-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.

Keywords

IL-6 Crohn’s disease adhesion molecule apoptosis 

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Hiroaki Ito
    • 1
  • Tomonori Hirotani
    • 1
  • Mitsunari Yamamoto
    • 1
  • Hiroyuki Ogawa
    • 1
  • Tadamitsu Kishimoto
    • 2
  1. 1.Department of Molecular MedicineOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Osaka UniversitySuitaJapan

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