• rheumatoid arthritis
• tumour necrosis factor α

Rheumatoid arthritis (RA) is a chronic disabling disease characterised by synovitis, destruction of cartilage and bone and, ultimately, loss of joint function. A great deal of research in rheumatology over the past two decades has focused on identifying cytokines and other mediators responsible for the inflammatory and degenerative processes in RA, with the aim of developing specific inhibitors or antagonists of therapeutic value. A key question in this research has been whether there is a degree of hierarchy in proinflammatory cytokine expression in RA, such that inhibiting the activity of a cytokine high up in the inflammatory cascade has an impact on the expression of downstream mediators of inflammation and joint damage.

Of the many cytokines thought to contribute to the inflammatory and degenerative changes that occur in RA, tumour necrosis factor α (TNFα) has emerged as being of major pathological significance. For example, TNFα was identified in the synovial membrane, and particularly at the cartilage-pannus junction, of patients with RA,1 and was found to be spontaneously produced by cultured synovial cells derived from RA patients.2 The in vitro properties of TNFα were also found to be consistent with a pathogenic role. Thus, TNFα promoted cartilage and bone resorption3 ,4 and induced the release of prostaglandin E₂ and collagenase by synovial cells.5 In addition, TNFα was reported to play a part in fibrosis6and to facilitate inflammatory cell infiltration by promoting the adhesion of neutrophils and lymphocytes to endothelial cells.7 ,8 Evidence was also provided to suggest that TNFα induces the production of interleukin 1 (IL1), another potential mediator of joint damage in RA,9 as antibodies to TNFα were shown to diminish the production of IL1 by rheumatoid synovium derived mononuclear cells.2 Using a similar experimental system, it was …