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Inhibition of IL-12 production by thalidomide.

TitleInhibition of IL-12 production by thalidomide.
Publication TypeJournal Article
Year of Publication1997
AuthorsMoller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Flockhart DA, Trinchieri G, Karp CL
JournalJ Immunol
Volume159
Issue10
Pagination5157-61
Date Published1997 Nov 15
ISSN0022-1767
KeywordsAntibodies, Monoclonal, Cells, Cultured, Humans, Immunosuppressive Agents, Indomethacin, Interleukin-10, Interleukin-12, Leukocytes, Mononuclear, Lymphocyte Activation, Monocytes, RNA, Messenger, Thalidomide, Transforming Growth Factor beta
Abstract

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.

Alternate JournalJ Immunol
PubMed ID9366446
Grant ListAI-01223 / AI / NIAID NIH HHS / United States
HL-45115 / HL / NHLBI NIH HHS / United States
P01-HL49545 / HL / NHLBI NIH HHS / United States

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