Cultured Synovial Cells: Differential Inhibition of COX-1 and COX-2 by Nonsteroidal Anti-inflammatory Drugs

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 43 (D 16). 1998;

Abstract: Hopital Universitaire Dupuytren Limoges Non-steroidal anti-inflammatory drugs (NSAIDs) act on the prostaglandin system via inhibition of cyclooxygenase (COX) enzymes: constitutive COX-1 with physiological functions and inducible COX-2 involved in the inflammatory response. Meloxicam a new NSAID has been shown to preferentially inhibit COX-2 and to have an improved gastro-intestinal safety profile. The objective of this study was to investigate the effect of meloxicam standard NSAIDs (piroxicam indomethacin diclofenac) and SC 58125 (highly selective inhibitor) on COX-1 and COX-2 activity. Adherent synovial cells were obtained by collagenase digestion of synovium isolated from osteoarthritis patients undergoing surgery. Between passages 3 and 6 cultured synovial cells were incubated with/without each NSAID for 30 min at 6 different concentrations. Interleukin-1 (IL-1 1 ng/ml) was/was not added for 6 h before incubation with NSAIDs. Unstimulated and IL-1-stimulated synovial cells were used to test NSAID action on COX-1 and COX-2 activity respectively. Supernatants were assayed for prostaglandin E2 (PGE2) by enzyme immunoassay. Basal PGE2 production was low and was increased by IL-1. The IC50 COX-1/COX-2 ratios for meloxicam diclofenac piroxicam indomethacin and SC 58125 were 16.2 2.5 0.1 0.1 and 37.8 respectively. Meloxicam and SC 58125 had an inhibitory activity 16- and 38-times more potent for COX-2 than for COX-1. Piroxicam and indomethacin were 9-times more active on COX-1 than on COX-2. The selective inhibition of COX-2 by meloxicam and SC 58125 has been confirmed in a human synovial cell culture system. le

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