• tumour necrosis factor
• rheumatology

Many biological functions are regulated through interactions of extracellular molecules with their cognate cell surface receptors. The transduction of these signals by their receptors at the plasma membrane to the intracellular machinery results in such cellular activities as gene activation, protein phosphorylation, cell proliferation, and cell destruction. Though the kinetics of these activities may differ, their interactions are coordinated by selective interplay between the receptors' intracellular domains and a select set of intracellular receptor binding proteins. One such family of extracellular molecules and their cell-surface receptors are the tumour necrosis factor (TNF) family of related cytokines and receptors, which is the topic of this review.

Rheumatoid arthritis, a disease of joint inflammation and destruction, is the result of inappropriate activation of resident and inflammatory cells within the synovial tissue. The consequence of an initiating and as yet unknown stimulus, the cascade of inflammatory processes are chronic and self perpetuating. The inflammation in the joints characteristic of arthritis is believed to be atrributable largely to misregulation of cytokine production, abnormal expression of receptors, or the absence of counter-regulatory pathways. Two proinflammatory cytokines, TNF and interleukin 1 (IL1), are believed to be the major cytokines cooperating in the pathology of this disease.1Therapeutic approaches that inhibit the interaction of these ligands with their receptors has been a successful avenue in the treatment of rheumatoid arthritis.2

One characteristic common to both TNF and IL1 is their ability to activate the transcription factor nuclear factor-kappa B (NF-κB), which is responsible for regulation of a number of genes necessary for the inflammation process.3 More recently, the elucidation of the TNF and IL1 signalling pathways has provided novel candidate molecules from which to develop therapeutic inhibitors that would block NF-κB activation. Furthermore, additional members of the TNF family have been discovered and are …