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IL-6 and Crohn's Disease

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Abstract:



Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. Its biological activities are shared by IL-6-family of cytokines such as leukemia inhibitory factor and oncostatin M. When IL-6 binds to IL-6R, the IL-6 / IL-6R complex then associates with gp130, the common signal transducer of cytokines related to IL-6. IL-6R does not have to be expressed on the cell surface for IL-6 signaling because soluble form of IL-6R (sIL-6R) can bind to IL-6 and function through gp130. Increased levels of IL-6 and sIL-6R have been demonstrated in both serum and intestinal tissues of the patients with active Crohn's disease. In animal model studies, anti-IL-6R monoclonal antibody (mAb) successfully prevented intestinal inflammation and systemic wasting disease by suppressing adhesion molecule expression by vascular endothelium. It also reduced colonic expression of tumor necrosis factor α, IL-1β, and interferon γmRNA without affecting the production of transforming growth factor β, IL-10, and IL-4. Moreover, the treatment displayed therapeutic efficacy against established colitis through the induction of lamina propria Tcell apoptosis. These results strongly suggest that specific targeting of IL-6 / sIL-6R pathway will be a promising new approach for the treatment of Crohn's disease, and the clinical trial of humanized anti-IL-6R mAb has been carried out.





Keywords: adhesion molecule; apoptosis; crohns disease; gp130; interleukin-6; monoclonal antibody; soluble interleukin-6 receptor; t cell

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/1568010033484296

Publication date: June 1, 2003

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