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.