In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene...

This volume of conference proceedings reviews the general pathophysiological significance of the isoforms of cyclooxygenase, and the likely value of selective COX-2 inhibitors in the treatment of rheumatoid conditions.

In 1971, Vane proposed that the mechanism of action of the aspirin-like drugs was through their inhibition of prostaglandin biosynthesis. Since then, there has been intense interest in the interaction between this diverse group of inhibitors and the enzyme known as cyclooxygenase (COX). It exists in two isoforms, COX-l and COX-2 (discovered some 5 years ago). Over the last two decades several new drugs have reached the market based on COX-l enzyme screens. Elucidation of the three-dimensional structure of COX-l has provided a new understanding for the actions of COX inhibitors. The...

The mainstay of therapy for rheumatoid disease is the non-steroid antiinflammatory drugs (NSAIDs), despite their inherent gastrointestinal toxicity and ability to cause renal damage in susceptible patients. The theory that the beneficial and toxic effects of NSAIDs stem from a reduction in prostanoid production through inhibition of cyclooxygenase implied that particular toxicities were inevitable with NSAIDs and would always be correlated with efficacy. However, over the years, it became apparent that at therapeutic doses, some NSAIDs had greater toxic side-effects than others, a fact not...

For the past 100 years the mainstay of therapy for rheumatoid arthritis (RA) has been aspirin or other drugs of the non-steroid anti-inflammatory group. In 1971 Vane pro posed that both the beneficial and toxic actions of these drugs was through inhibition of prostaglandin synthesis. The recent discovery that prostaglandins responsible for pain and other symptoms at inflammatory foci are synthesized by an inducible cyclooxygenase (COX-2) that is encoded by a gene distinct from that of the consti tutive enzyme (COX-I) provided a new target for therapy of RA. A drug that would selectively...

In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non- invasive indicator. Significant progress has been made towards the characterization of the leukotriene...