Cytokine expression and networks in rheumatoid arthritis: rationale for anti-TNF alpha antibody therapy and its mechanism of action.
The cloning of cytokine cDNAs has permitted the analysis of cytokine expression in diseased sites such as rheumatoid joints. A very wide range of cytokines were detected, mostly with proinflammatory activities. From the analysis of cytokine regulation in rheumatoid joint cell cultures using neutralizing anti-cytokine antibodies, it was found that blockade of TNF alpha reduced the production of other proinflammatory cytokines. Hence TNF alpha was a potential therapeutic target. This concept was tested successfully in collagen induced arthritis in mice and led to clinical trials of anti-TNF alpha antibody in rheumatoid arthritis (RA) in humans. The mechanism of action of anti-TNF alpha will be discussed.
Kennedy Institute of Rheumatology, Sunley Division, Hammersmith, London, U.K.
M
M
Feldmann
F M
FM
Brennan
R O
RO
Williams
M J
MJ
Elliott
R N
RN
Maini
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha