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Potent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance.

TitlePotent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance.
Publication TypeJournal Article
Year of Publication1998
AuthorsKarp CL, Wysocka M, Ma X, Marovich M, Factor RE, Nutman T, Armant M, Wahl L, Cuomo P, Trinchieri G
JournalEur J Immunol
Volume28
Issue10
Pagination3128-36
Date Published1998 10
ISSN0014-2980
KeywordsCells, Cultured, Dendritic Cells, Humans, Immune Tolerance, Interleukin-10, Interleukin-12, Lipopolysaccharides, Monocytes, Transcription, Genetic, Transforming Growth Factor beta
Abstract

Endotoxin tolerance, the down-regulation of a subset of endotoxin-driven responses after an initial exposure to endotoxin, may provide protection from the uncontrolled immunological activation of acute endotoxic shock. Recent data suggest, however, that the inhibition of monocyte/macrophage function associated with endotoxin tolerance can lead to an inability to respond appropriately to secondary infections in survivors of endotoxic shock. IL-12 production by antigen-presenting cells is central to the orchestration of both innate and acquired cell-mediated immune responses to many pathogens. IL-12 has also been shown to play an important role in pathological responses to endotoxin. We therefore examined the regulation of IL-12 during endotoxin tolerance. Priming doses of lipopolysaccharide ablate the IL-12 productive capacity of primary human monocytes. This suppression of IL-12 production is primarily transcriptional. Unlike the down-regulation of TNF-alpha under such conditions, the mechanism of IL-12 suppression during endotoxin tolerance is not dependent upon IL-10 or transforming growth factor-beta, nor is IL-12 production rescued by IFN-gamma or granulocyte-macrophage colony-stimulating factor. Of note, human dendritic cells also undergo endotoxin tolerance, with potent down-regulation of IL-12 production. Endotoxin tolerance-related suppression of IL-12 production provides a likely mechanism for the anergy seen during the immunological paralysis which follows septic shock.

DOI10.1002/(SICI)1521-4141(199810)28:10<3128::AID-IMMU3128>3.0.CO;2-T
Alternate JournalEur J Immunol
PubMed ID9808181
Grant ListAI40507 / AI / NIAID NIH HHS / United States
CA20833 / CA / NCI NIH HHS / United States
DE12167 / DE / NIDCR NIH HHS / United States

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