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Monocyte Human Leukocyte Antigen–DR Transcriptional Downregulation by Cortisol during Septic Shock

2004; American Thoracic Society; Volume: 169; Issue: 10 Linguagem: Inglês

10.1164/rccm.200309-1329oc

1535-4970

Yves Le Tulzo, Céline Pangault, Laurence Amiot, Valérie Guilloux, Olivier Tribut, C. Arvieux, Christophe Camus, R Fauchet, R. Thomas, Bernard Drénou,

Immune Response and Inflammation

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.