Effects of meloxicam, compared with other NSAIDs, on cartilage proteoglycan metabolism, synovial prostaglandin E2, and production of interleukins 1, 6 and 8, in human and porcine explants in organ culture.
Some non-steroidal anti-inflammatory drugs (NSAIDs) can accelerate joint damage in osteoarthritis by enhancing the production of pro-inflammatory cytokines or inhibiting cartilage proteoglycan synthesis. Meloxicam, 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 E2 (PGE2) and interleukins 1 and 6 by human synovial tissue explants in-vitro. Meloxicam at submicromolar concentrations inhibited synovial PGE2 production but, up to therapeutic drug concentrations (< or = 4 microM), did not affect synovial production of the pro-inflammatory cytokine IL-1. In contrast, hydrocortisone, 10 microM, a positive control, inhibited release of this cytokine, and indomethacin, 100 microM, increased its production. The lack of effects of meloxicam were evident irrespective of intrinsic IL-1 bioactivity of the synovia, production of IL-1 inhibitors or time of incubation. Production of the part anti-inflammatory cytokine IL-6, was significantly increased by therapeutic concentrations of meloxicam, as well as by indomethacin. Another major pro-inflammatory cytokine, IL-8, was unaffected by therapeutic concentrations of meloxicam. Meloxicam, 0.1-4.0 microM, did not affect cartilage proteoglycan production whereas indomethacin, 100 microM, significantly reduced synthesis of these macromolecules. Thus meloxicam, at concentrations within the therapeutic range and at which pronounced inhibition of prostaglandin production is evident, affects neither cartilage proteoglycan production nor the production of those cytokines likely to be important in cartilage destruction.
Rainsford
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KD
Division of Biomedical Sciences, School of Science and Mathematics, Sheffield Hallam University, UK.
Ying
C
C
Smith
F C
FC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D000077239:Meloxicam; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D013552:Swine; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D011509:Proteoglycans; D013843:Thiazines; D013844:Thiazoles; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077239:Meloxicam; D006854:Hydrocortisone; D007213:Indomethacin