Enhanced prostaglandin E2 secretion by cytokine-stimulated human synoviocytes in the presence of subtherapeutic concentrations of nonsteroidal antiinflammatory drugs

Human synoviocytes were stimulated for 48 hours or 72 hours with cytokines (recombinant interleukin-1 beta and/or recombinant tumor necrosis factor alpha) in the presence or absence of selected nonsteroidal antiinflammatory drugs. The drugs were tested at subtherapeutic and clinically therapeutic levels, as follows: piroxicam 0.3 pM to 3 X 10(6) pM, sodium salicylate 30 nM to 3 X 10(6) nM, and indomethacin 3 pM to 3 X 10(6) pM. At low concentrations, all 3 drugs showed significant enhancement of prostaglandin E2 (PGE2) secretion (piroxicam, salicylate greater than indomethacin). At high, clinically therapeutic concentrations, all drugs showed suppression of PGE2 secretion (indomethacin greater than piroxicam greater than salicylate). The enhancement of PGE2 secretion may be partially responsible for the flare of arthralgia or arthritis frequently seen after termination of drug therapy.