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Publication Detail
Therapeutic actions of cyclosporine and anti-tumor necrosis factor α in collagen-induced arthritis and the effect of combination therapy
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Williams RO, Mauri C, Mason LJ, Marinova-Mutafchieva L, Ross SE, Feldmann M, Maini RN
  • Publication date:
  • Pagination:
    1806, 1812
  • Journal:
    Arthritis and Rheumatism
  • Volume:
  • Issue:
  • Status:
  • Print ISSN:
Objective. To define the mechanisms of action of 2 novel drugs, cyclosporine and anti-tumor necrosis factor α (TNFα), in collagen-induced arthritis and to determine the effect of combination therapy. Methods. Type II collagen-immunized DBA/1 mice with established arthritis were treated with cyclosporine alone, anti-TNFα alone, cyclosporine plus anti-TNFα, or saline. Results. Cyclosporine was found to ameliorate arthritis, suppress interferon-γ (IFNγ) production by CD4+ T cells, and reduce TNFα expression in arthritic joints. However, cyclosporine did not directly inhibit TNFα production by macrophages, indicating that the decrease in TNFα expression observed in vivo was probably an indirect consequence of the reduction in type 1 T helper cell activity. Anti-TNFα also reduced IFNγ production by T cells, indicating that TNFα is involved in the cellular immune response to collagen. Combined treatment with cyclosporine plus anti-TNFα had an additive therapeutic effect. Conclusion. Although cyclosporine and anti- TNFα target different points in the inflammatory pathway, there is an overlap in the consequences of their actions in vivo.
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