Possible background mechanisms of the effectiveness of cyclooxygenase-2 inhibitors in the treatment of rheumatoid arthritis.

Abstract

Cyclooxygenase (COX)-2 was induced in an acute exudative inflammatory model (rat carrageenin-induced pleurisy) in which prostaglandin E2, 6-keto-prostaglandin F1alpha, and thromboxane B2 were generated in the pleural fluid. Selective COX-2 inhibitors, such as NS-398, inhibited the plasma exudation and generation of prostaglandin E2, but not that of thromboxane B2 and 6-keto-prostaglandin F1alpha, in the pleural fluid. In proliferative inflammatory models, COX-2 was induced, and selective COX-2 inhibitors suppressed granuloma formation, particularly, microvessel formation. COX-2 was induced during angiogenesis in a sponge model implanted into skin of rat, and the COX-2 inhibitor suppressed the angiogenesis. As induction of COX-2 was reported in osteoblasts, COX-2 was involved in most characteristic responses of acute exudative inflammation, granuloma formation, bone resorption, and pain in rheumatoid arthritis. The prevention of these COX-2 responses provides a rationale for the effectiveness of COX-2 inhibitors in the treatment of rheumatoid arthritis.