Open Access Highly Accessed Research article

Anti-TNF-α antibody allows healing of joint damage in polyarthritic transgenic mice

David J Shealy1*, Paul H Wooley2, Eva Emmell1, Amy Volk1, Amy Rosenberg1, George Treacy1, Carrie L Wagner1, Lois Mayton2, Don E Griswold1 and Xiao-yu R Song1

Author Affiliations

1 Centocor, Inc, Malvern, Pennsylvania, USA

2 Department of Orthopaedic Surgery, Wayne State University Medical School, Detroit, Michigan, USA

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Arthritis Res 2002, 4:R7  doi:10.1186/ar430

Published: 28 June 2002

Abstract

Anti-tumor-necrosis-factor-α (TNF-α) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-α (hTNF-α) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-α antibody was assessed using various pathological indicators of disease progression. The clinical severity of arthritis in Tg197 mice was significantly reduced after anti-TNF-α treatment in comparison with saline-treated mice and in comparison with baseline assessments in both young and aged mice. The treatment with anti-TNF-α prevented loss of body weight. Inflammatory pathways as reflected by elevated circulating hTNF-α and local expression of various proinflammatory mediators were all diminished by anti-TNF-α treatment, confirming a critical role of hTNF-α in this model of progressive polyarthritis. More importantly, the amelioration of the disease was associated with reversal of existing structural damage, including synovitis and periosteal bone erosions evident on histology. Repair of cartilage was age dependent: reversal of cartilage degradation after anti-TNF-α treatment was observed in young mice but not in aged mice.

Keywords:
antibody; animal models; cytokines; rheumatoid arthritis; tumor necrosis factor alpha