Inhibition of IL-12 production by thalidomide.
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.
Moller
D R
DR
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dmoller@welchlink.welch.jhu.edu
Wysocka
M
M
Greenlee
B M
BM
Ma
X
X
Wahl
L
L
Flockhart
D A
DA
Trinchieri
G
G
Karp
C L
CL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D013792:Thalidomide; D007213:Indomethacin