POSSIBLE BACKGROUND MECHANISMS OF THE EFFECTIVENESS OF CYCLOOXYGENASE-2 INHIBITORS IN THE TREATMENT OF RHEUMATOID-ARTHRITIS

Cyclooxygenase (COX)-2 was induced in an acute exudative inflammatory model (rat carrageenin-induced pleurisy) in which prostaglandin E-2, 6 -keto-prostaglanin Fl,, and thromboxane B-2 were generated in the pleu ral fluid. Selective COX-2 inhibitors, such as NS-398, inhibited the p lasma exudation and generation of prostaglandin E-2, but not that of t hromboxane B2 and 6-keto-prostaglandin F-1 alpha, in the pleural fluid . In proliferative inflammatory models, COX-2 was induced, and selecti ve COX-2 inhibitors suppressed granuloma formation, particularly, micr ovessel formation. COX-2 was induced during angiogenesis in a sponge m odel implanted into skin of rat, and the COX-2 inhibitor suppressed th e angiogenesis. As induction of COX-2 was reported in osteoblasts, COX -2 was involved in most characteristic responses of acute exudative in flammation, granuloma formation, bone resorption, and pain in rheumato id arthritis. The prevention of these COX-2 responses provides a ratio nale for the effectiveness of COX-2 inhibitors in the treatment of rhe umatoid arthritis.