NOVEL, NONTRADITIONAL, NONSTEROIDAL, ANTIINFLAMMATORY AGENTS

Traditional, non-steroidal anti-inflammatory agents (NSAIAs) are arach idonate metabolite related. Since arachidonate metabolites do not indu ce the whole range of inflammatory responses, their blockade does not produce anti-inflammatory actions as potent as those of the corticoste roids. The recent development of cytokine research reveals the wide ra nge involvement of IL-1, IL-6 and tumour necrosis factor (TNF) in the inflammatory process. Therefore, cytokine antagonists produce the most effective means of treatment for inflammatory disorders and are as ef fective, or even more potent, than corticosteroids, without producing the side effects common to such compounds. The only IL-1 blocker avail able today is the natural IL-1 receptor antagonist (IL-1 RA), a polype ptide which is easily metabolised in the bloodstream with a very short half-life (21 minutes). Thus, active research has been carried out to develop stable, long-acting agents which can be taken by oral adminis tration or by parenteral injections rather than by intravenous infusio n, which is required for IL-1 RA. A number of compounds which inhibit cytokine receptors, cytokine production, cytokine release, and/or cyto kine converting enzymes will be reviewed. It is anticipated that safe and effective synthetic anti-inflammatory drugs will be developed in t he near future.