EFFECTS OF MELOXICAM, COMPARED WITH OTHER NSAIDS, ON CARTILAGE PROTEOGLYCAN METABOLISM, SYNOVIAL PROSTAGLANDIN E-2, AND PRODUCTION OF INTERLEUKIN-1, INTERLEUKIN-6 AND INTERLEUKIN-8, IN HUMAN AND PORCINE EXPLANTS IN ORGAN-CULTURE

Some non-steroidal anti-inflammatory drugs (NSAIDs) can accelerate joi nt damage in osteoarthritis by enhancing the production of pro-inflamm atory cytokines or inhibiting cartilage proteoglycan synthesis. Meloxi cam, a new NSAID, was compared with standard NSAIDs for its effect on proteoglycan synthesis and degradation in human and porcine cartilage explants, as well as the production of prostaglandin E-2 (PGE(2)) and interleukins 1 and 6 by human synovial tissue explants in-vitro. Melox icam at submicromolar concentrations inhibited synovial PGE(2) product ion but, up to therapeutic drug concentrations (less than or equal to 4 mu M), did not affect synovial production of the pro-inflammatory cy tokine IL-1. In contrast, hydrocortisone, 10 mu M, a positive control, inhibited release of this cytokine, and indomethacin, 100 mu M, incre ased its production. The lack of effects of meloxicam were evident irr espective of intrinsic IL-I bioactivity of the synovia, production of IL-1 inhibitors or time of incubation. Production of the part antiinfl ammatory cytokine IL-6, was significantly increased by therapeutic con centrations of meloxicam, as well as by indomethacin. Another major pr o-inflammatory cytokine,IL-8, was unaffected by therapeutic concentrat ions of meloxicam. Meloxicam, 0.1-4.0 mu M, did not affect cartilage p roteoglycan production whereas indomethacin, 100 mu M, significantly r educed synthesis of these macromolecules. Thus meloxicam, at concentra tions within the therapeutic range and at which pronounced inhibition of prostaglandin production is evident, affects neither cartilage prot eoglycan production nor the production of those cytokines likely to be important in cartilage destruction.