In vitro effects of NSAIDs and corticosteroids on the synthesis and secretion of interleukin 1 by human osteoarthritic synovial membranes.
The mechanism(s) of action of NSAIDs and corticosteroids in arthritic diseases has been the subject of intensive investigation in recent years. Although NSAIDs and corticosteroids have many effects, their possible ability to modify the disease course in patients has not been fully documented. In an attempt to characterize the mechanism(s) involved in the effect of some NSAIDs in joint diseases, we investigated the effect of three concentrations within the pharmacological (260 micrograms/ml) and therapeutic (26 and 2.6 micrograms/ml) ranges of tiaprofenic acid in the synthesis and release of interleukin (IL-1) alpha and beta in human OA synovial membranes. The effect of tiaprofenic acid was compared to the effect of two other NSAIDs, sodium salicylate (160 micrograms/ml) and indomethacin (1.5 micrograms/ml), and to a corticosteroid, hydrocortisone (0.725 and 7.25 micrograms/ml). This study was carried out using human OA synovium explants incubated in the presence or absence of LPS. In the absence of LPS and at therapeutic concentration, tiaprofenic acid decreased both the synthesis and release of IL-1 beta. A less marked effect of the drug was noted under LPS treatment, and inhibition of the production/secretion of IL-1 beta was found only at pharmacological concentration. Sodium salicylate and indomethacin did not share this action, and demonstrated either no effect or enhancement of IL-1 beta synthesis, respectively, in the presence of LPS. As expected, hydrocortisone demonstrated a marked decrease on IL-1 alpha and IL-1 beta, both in the presence and absence of LPS. These results bring forth new information on the action of these drugs and their effects on the OA pathophysiological process.
Pelletier
J P
JP
University of Montreal, Canada.
Cloutier
J M
JM
Martel-Pelletier
J
J
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D012980:Sodium Salicylate / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011422:Propionates; C021270:tiaprofenic acid; D006854:Hydrocortisone; D012980:Sodium Salicylate; D007213:Indomethacin