THE EFFECT OF ANTIRHEUMATIC DRUGS ON INTERLEUKIN-1 (IL-1) ACTIVITY AND IL-1 AND IL-1 INHIBITOR PRODUCTION BY HUMAN MONOCYTES

Abstract

Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. The objective of our study was to investigate the effect of a number of representative antirheumatic agents on the activity of IL-1 and the production of both IL-1 and IL-1 inhibitor by human monocytes. IL-1 activity and production were measured by its effect on the proliferation of murine thymocytes; IL-1 inhibitor production was assayed by inhibition of IL-1 mediated thymocyte proliferation. Dexamethasone (10-100 nM) inhibited IL-1 production and IL-1 mediated thymocyte proliferation. High concentrations of indomethacin, aspirin, and 12 other nonsteroidal antiinflammatory drugs (NSAID) inhibited IL-1 activity, or production or both. Methotrexate inhibited IL-1 activity without affecting IL-1 production. D-penicillamine inhibited IL-1 activity and tended to inhibit IL-1 production. Gold compounds inhibited IL-1 activity, but only auranofin inhibited IL-1 production. Acetaminophen in high concentrations (1 mg/ml) inhibited IL-1 activity and production. Colchicine inhibited IL-1 activity but not IL-1 production. No drug tested induced, by itself, the production of IL-1 inhibitor or enhanced the production of IL-1 inhibitor.