Abstract
Piroxicam and other antiarthritic drugs were compared with respect to their effects on T-lymphocyte/monocyte/rheumatoid synovial cell interactions leading to inflammatory mediator production. Piroxicam inhibited PGE2 formation by blood mononuclear cells, but was less potent than indomethacin. Both drugs enhanced suboptimal phytohemagglutinin (PHA)-stimulated tritiated thymidine (3H-TdR) incorporation by mononuclear cells, although optimal responses were less affected. Exogenous interleukin-2 (IL-2) enhanced suboptimal but not optimal PHA responses, and the effects of the cyclo-oxygenase inhibitors were overcome by exogenous PGE2, Thus piroxicam and indomethacin prevented the inhibition by endogenous monocyte-derived PGE2 of IL-2 secretion and activity. Other antiarthritic drugs, including antimalarials, immunosuppressive agents and gold salts, inhibited PHA-induced lymphocyte proliferation regardless of the level of stimulation. Mepacrine and chioroquine were more effective in inhibiting the release of mononuclear cell factor (MCF) that stimulated PGE2 synthesis by synovial cells. Cyclosporin-A, azathioprine and 6-mercaptopurine were more potent as antiproliferative agents than as inhibitors of mediator release. Sodium aurothiomalate and aurothioglucose selectively interfered with lymphocyte-mediated amplification of MCF release, whereas auranofin inhibited spontaneous production of monocytes and the action of MCF on synovial cells. In rheumatoid synovial cells, piroxicam and indomethacin inhibited PGE2 production but not collagenase release. Suppression of MCF release could lead indirectly to reduction of IL-2 and collagenase as well as PGE2 production and consequently to more profound inhibition of immunologically-mediated inflammation.
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Gordon, D., Lewis, G.P. Effects of piroxicam on mononuclear cells. Inflammation 8 (Suppl 1), S87–S102 (1984). https://doi.org/10.1007/BF00915716
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DOI: https://doi.org/10.1007/BF00915716