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Am J Respir Crit Care Med. 2002 Dec 1;166(11):1475-82. Epub 2002 Aug 15.

Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock.

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  • 1Department of Internal Medicine, Division of Medical Intensive Care, and Faculty of Medicine, University Hospital of Geneva, Switzerland.

Abstract

Monocytes from many critically ill patients show a low level of major histocompatibility complex type II (MHC II) expression. This phenomenon is believed to play a role in these patients' increased susceptibility to secondary infections. In the present study, we show that the level of monocyte human leukocyte antigen (HLA)-DR expression inversely correlates with the degree of severity of the sepsis syndrome. The defect of the monocyte HLA-DR expression resides in an intracellular sequestration of the MHC II molecules, a posttranslational effect. No significant decrease in the rate of transcription of HLA-DR, or its major transcriptional inducer, Class II transactivator, was noted. The levels of HLA-DR protein produced by monocytes from patients with septic shock were comparable to those from healthy volunteers. Plasma from patients with septic shock induced significant HLA-DR endocytosis resulting in decreased surface HLA-DR expression of normal donor monocytes. This effect was partially blocked by anti-interleukin (IL)-10 monoclonal antibody, but not by antagonists to transforming growth factor-beta1, prostaglandins, or beta-adrenergic agonists. Altogether, these data suggest that HLA-DR molecules are re-endocytosed and retained intracellularly in monocytes from patients with septic shock, and that this phenomenon is partially mediated by IL-10. IL-10 may represent a future target for immunomodulating patients with the sepsis syndrome or critically ill patients at risk of developing infections.

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PMID:
12406851
[PubMed - indexed for MEDLINE]
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