To evaluate the effect of therapeutic and pharmacologic concentrations of two non-steroidal anti-inflammatory drugs (NSAIDs), nimesulide and naproxen, on the synthesis of urokinase (uPA), plasminogen activator inhibitor (PAI-1) and interleukin-6 (IL-6) in human synovial fibroblasts isolated from osteoarthritis (OA) patients.
Urokinase, PAI-1, and IL-6 production were measured by specific ELISA.
Nimesulide and naproxen induced a dose-dependent decrease in uPA 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.
The results of this study indicate some of the mechanisms by which nimesulide and naproxen could exert their effects on the arthritis process. The suppressive action of the two drugs on the synthesis of uPA, while stimulating PAI-1 production, may have a positive impact on the balance of plasminogen activator/inhibitor, which could help reduce cartilage catabolism.