Therapeutic modulation of cytokines.

The potent 'proarthritic' effects of cytokines such as interleukin-1 (IL-1), IL-6, tumour necrosis factor a (TNFa) on cells and isolated connective tissues,' the ability to induce synovitis by local injection of cytokines,2 and the ability to block the pathology of experimental models of arthritis by anticytokine reagents3 4 strongly argue that these potent local hormones play a key role in the pathology of chronic arthritic conditions such as rheumatoid arthritis (RA) and septic arthritis. It is not surprising, therefore, that the cytokines are perceived as major therapeutic targets in these conditions. The first faltering attempts to develop anticytokine agents started only a short time ago, in the mid 1980s, but through the growth in the biopharmaceutical industry in the past decade we currently have a number of anticytokine agents in clinical trials. This paper will consider briefly the methods used to modulate cytokines, and interested readers should refer to recent reviews for more details.5 6