|Potent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance.
|Year of Publication
|Karp CL, Wysocka M, Ma X, Marovich M, Factor RE, Nutman T, Armant M, Wahl L, Cuomo P, Trinchieri G
|Eur J Immunol
|Cells, Cultured, Dendritic Cells, Humans, Immune Tolerance, Interleukin-10, Interleukin-12, Lipopolysaccharides, Monocytes, Transcription, Genetic, Transforming Growth Factor beta
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.
|Eur J Immunol
|AI40507 / AI / NIAID NIH HHS / United States
CA20833 / CA / NCI NIH HHS / United States
DE12167 / DE / NIDCR NIH HHS / United States
Submitted by mam2155 on March 24, 2014 - 4:16pm