The role of cytokines in the pathogenesis of rheumatoid arthritis.

Recombinant DNA technology has made it possible to identify the cytokines expressed in the joints of people with active rheumatoid arthritis (RA). Because a large number of cytokines are expressed in the rheumatoid synovium and many of these cytokines may have redundant biological functions, it was necessary to study cytokine regulation to identify potential therapeutic targets. The regulation of interleukin 1, a proven inducer of bone and cartilage destruction in the rheumatoid synovium, was thus studied and anti-tumour necrosis factor alpha (anti-TNF-alpha) antibody was found to reduce its synthesis markedly, as well as that of other cytokines, leading to our proposal of TNF-alpha as a therapeutic target. The further study of clinical trials in RA verified that the mechanism of action of anti-TNF-alpha includes the down-regulation of several pro-inflammatory agents, diminished leucocyte recruitment and possibly regulation of angiogenesis.