Evaluation of antirheumatic drugs for their effect in vitro on purified human synovial fluid phospholipase A2.
Agents used to treat rheumatoid arthritis were examined for their ability to modify synovial fluid phospholipase A2 (SF-PLA2) activity. Nonsteroidal or steroidal antiinflammatory drugs and disease modifying agents exhibited little or no PLA2 modulatory activity. The exceptions include weak inhibition displayed by the cyclooxygenase inhibitors, indomethacin (IC50 = 144.8 microM) and sulindac sulfide (30.2 microM) and a 5-lipoxygenase translocation inhibitor, MK-886 (IC50 = 50 microM). Cyclosporine potentiated acylhydrolysis (EC50 = 1.5 microM) whereas the other immunomodulators examined demonstrated no significant effect on SF-PLA2 activity. Our data show that there are no selective PLA2 inhibitors currently used in the treatment of human arthritic disease and the viability of this novel approach remains to be tested.
Marshall
L A
LA
Division of Immunopharmacology, Wyeth Ayerst Research, Princeton, NJ.
Bauer
J
J
Sung
M L
ML
Chang
J Y
JY
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D013582:Synovial Fluid / Q000201:enzymology*
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003524:Cyclosporins; D010741:Phospholipases A; D054467:Phospholipases A2