TNF blockade in rheumatoid arthritis: implications for therapy and pathogenesis.
The role of the immune response in rheumatoid arthritis (RA) is a subject of debate, although it is widely believed to be a T-cell-driven disease. Progress is being hindered by lack of convincing evidence of a defined specific antigen initiating or perpetuating the response. Clinical trials using monoclonal antibodies directed against T-cell surface molecules such as CD4. CD5, and CD7 have thus far not provided evidence of efficacy. The negative data may reflect inadequate dosing or could suggest that indiscriminate depletion of T cells is insufficient by itself as a therapeutic strategy. Blocking proinflammatory cytokines (e.g. TNF alpha, IL-1) or augmenting anti-inflammatory cytokines (e.g. IL-10) offers an alternative approach to therapy. Clinical trials using monoclonal anti-TNF alpha have been particularly successful in controlling inflammation and markedly reducing acute phase proteins and cellular ingress. However, because disease invariably relapses, repeated therapy is necessary. Preliminary experience suggests that this is possible. Anti-TNF therapy for RA has defined a molecular target and new approach for treating immuno-inflammatory disorders.
Maini
R N
RN
Kennedy Institute of Rheumatology, London, UK.
Elliott
M
M
Brennan
F M
FM
Williams
R O
RO
Feldmann
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D019011:Antigens, CD7 / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D015704:CD4 Antigens; D018956:CD5 Antigens; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10