INHIBITION OF IL-12 PRODUCTION BY THALIDOMIDE

The immunomodulatory properties of thalidomide are currently being exp loited therapeutically in conditions as diverse as erythema nodosum le prosum, chronic graft-vs-host disease, rheumatoid arthritis, and sarco idosis. The relevant mechanism of action of thalidomide in these disea ses remains unclear, The important role recently ascribed to IL-12, a cytokine critical to the development of cellular immune responses, in the pathogenesis of several of these conditions led us to examine whet her thalidomide affects the production of IL-12, Thalidomide potently suppressed the production of IL-12 from human PBMC and primary human m onocytes in a concentration-dependent manner. Thalidomide-induced inhi bition of IL-12 production was additive to that induced by suboptimal inhibiting doses of dexamethasone, and occurred by a mechanism indepen dent of known endogenous inhibitors of IL-12 production. These results suggest that thalidomide may have therapeutic utility in a wide range of immunologic disorders that are characterized by inappropriate cell ular immune responses.