Inhibition of IL-12 Production by Thalidomide

Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
The Journal of Immunology (Impact Factor: 4.92). 12/1997; 159(10):5157-61.
Source: PubMed


The immunomodulatory properties of thalidomide are currently being exploited therapeutically in conditions as diverse as erythema nodosum leprosum, chronic graft-vs-host disease, rheumatoid arthritis, and sarcoidosis. The relevant mechanism of action of thalidomide in these diseases 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 whether thalidomide affects the production of IL-12. Thalidomide potently suppressed the production of IL-12 from human PBMC and primary human monocytes in a concentration-dependent manner. Thalidomide-induced inhibition of IL-12 production was additive to that induced by suboptimal inhibiting doses of dexamethasone, and occurred by a mechanism independent 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 cellular immune responses.

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    • "Here, we also detected downregulation of TNF-α production by LPS-stimulated MΦ after thalidomide treatment. Furthermore, we found also that IL-12 production by unstimulated cultured LC was strongly suppressed by both concentrations of thalidomide, and that IL-12 secretion by LPS-stimulated MΦ was reduced by high concentrations of thalidomide (10-6 M), supporting previous studies showing that thalidomide inhibits IL-12 production by LPS-stimulated monocytes [25]. Another study suggested suppression of TNF-α and IL-12 as a possible mechanism of thalidomide's clinical effects in Crohn's disease, which improves clinical symptoms in patients [26], what may explain its clinical efficacy. "
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