Preferential inhibition of cyclooxygenase-2 by meloxicam in human rheumatoid synoviocytes

The aim of this study was to evaluate the anti-inflammatory effect of 4-hyd roxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1,2-benzothiazine-3-carboxamide-1 ,l-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like c ells (synoviocytes). Synoviocytes were treated with meloxicam in the presen ce or absence of interleukin-1 beta. Meloxicam had no effect on both cycloo xygenase-l and -2 expression as determined by Western blot analysis, immuno histochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 act ivity, but only the higher doses of meloxicam inhibited cyclooxygenase-l ac tivity as determined by prostaglandin E-2 synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxyg enase-l on cultured rheumatoid synoviocytes without affecting cyclooxygenas e expression. On the other hand, indomethacin had no selectivity and dexame thasone inhibited the expression of cyclooxygenase-2. Our data indicate tha t clinical efficacy and safety of meloxicam for rheumatoid arthritis may re sult from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-l on rheumatoid synoviocytes. (C) 2000 Elsevier Science B.V. All rights reserved.