2 NSAID, NIMESULIDE AND NAPROXEN, CAN REDUCE THE SYNTHESIS OF UROKINASE AND IL-6 WHILE INCREASING PAI-1, IN HUMAN OA SYNOVIAL FIBROBLASTS

Objectives, To evaluate the effect of therapeutic and pharmacologic co ncentrations of two non-steroidal anti-inflammatory drugs (NSAIDs), ni mesulide and naproxen, on the synthesis of urokinase (uPA), plasminoge n activator inhibitor (PAI-1) and interleukin-6 (IL-6) in human synovi al fibroblasts isolated from osteoarthritis (OA) patients. Methods: Ur okinase, PAI-I, and IL-6 production were measured by specific ELISA, R esults: Nimesulide and naproxen induced a dose-dependent decrease in u PA synthesis. The two drugs, at therapeutic concentrations, exerted a stimulatory effect on the synthesis of PAI-1 whereas the synthesis of IL-6 was significantly reduced by both NSAIDs. Conclusion: The results of this study indicate some of the mechanisms by which nimesulide and naproxen could exert their effects on the arthritic process, The supp ressive action of the two drugs on the synthesis of uPA, while stimula ting PAI-1 production, may have a positive impact on the balance of pl asminogen activator/inhibitor which could help reduce cartilage catabo lism.