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Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis

Bailin Liang1 email, Zheng Song3 email, Bin Wu3 email, Debra Gardner2 email, David Shealy2 email, Xiao-Yu Song4 email and Paul H Wooley3 email

Department of Combination Products, Vistakon, 7500 Centurion Parkway, Jacksonville, FL 32256, USA

Department of Immunobiology, Centocor, 145 King of Prussia Road, Radnor, PA 19087, USA

Orthopaedic Research Institute, 929 North St. Francis, Wichita, Kansas 67214, USA

Department of Biosurgicals, Ethicon, Research & Development, Route 22 West, PO Box 151, Somerville, NJ 08876, USA

author email corresponding author email

Journal of Inflammation 2009, 6:10doi:10.1186/1476-9255-6-10

Published: 15 April 2009

Abstract

Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus) and erosive (erosions and architecture) parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.


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