PHARMACOLOGICAL AND BIOCHEMICAL DEMONSTRATION OF THE ROLE OF CYCLOOXYGENASE-2 IN INFLAMMATION AND PAIN

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the t reatment of inflammatory diseases, but significant side effects such a s gastrointestinal erosion and renal damage limit their use, NSAIDs in hibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified-COX-1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an ani mal model of acute inflammation (injection of carrageenan into the foo tpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC-581 25) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric t oxicity, These data suggest that selective inhibition of COX-2 may pro duce superior antiinflammatory drugs with substantial safety advantage s over existing NSAIDs.