Cytokine expression and networks in rheumatoid arthritis: rationale for anti-TNF alpha antibody therapy and its mechanism of action.
Feldmann M., Brennan FM., Williams RO., Elliott MJ., Maini RN.
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.