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Comparative Study
. 2004 May 15;169(10):1144-51.
doi: 10.1164/rccm.200309-1329OC. Epub 2004 Mar 17.

Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock

Yves Le Tulzo  1 , Celine Pangault, Laurence Amiot, Valérie Guilloux, Olivier Tribut, Cédric Arvieux, Christophe Camus, Renée Fauchet, Rémi Thomas, Bernard Drénou
Affiliations
Comparative Study

Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock

Yves Le Tulzo et al. Am J Respir Crit Care Med. .

Abstract

Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen-DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomenon in septic patients. We confirmed the early loss of monocyte HLA-DR expression in all infected patients and demonstrated that this persistent lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. Furthermore, these abnormalities correlated with the high cortisol levels observed in sepsis and not with those of other putative factors such as catecholamines or interleukin-10. Finally, in vitro studies evidenced that glucocorticoids decrease HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by down modulating its isoforms I and III. We conclude that in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with a poor outcome. We suggest that the high endogenous cortisol level observed in septic shock may be a possible new factor involved in the loss of HLA-DR expression on monocytes via its effect on HLA-DR and CIITA transcription.

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