Open AccessTherapeutic actions of cyclosporine and anti‐tumor necrosis factor α in collagen‐induced arthritis and the effect of combination therapy
Author(s) -
Williams Richard O.,
Mauri Claudia,
Mason Lesley J.,
MarinovaMutafchieva Lilia,
Ross Susan E.,
Feldmann Marc,
Maini Ravinder N.
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199810)41:10<1806::aid-art12>3.0.co;2-9
Subject(s) - tumor necrosis factor alpha , in vivo , arthritis , medicine , cytokine , immunology , combination therapy , immune system , interferon , tumor necrosis factor α , necrosis , cancer research , pharmacology , biology , microbiology and biotechnology
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.