Le Tulzo Yves, Pangault Celine, Amiot Laurence, Guilloux Valérie, Tribut Olivier, Arvieux Cédric, Camus Christophe, Fauchet Renée, Thomas Rémi, Drénou Bernard
Service de Réanimation Médicale et des Maladies Infectieuses, Laboratoire d'Hématologie et de Biologie des Cellules Sanguines UPRES-EA 22-33, Centre Hospitalier Universitaire de Rennes, Rennes, France.
Am J Respir Crit Care Med. 2004 May 15;169(10):1144-51. doi: 10.1164/rccm.200309-1329OC. Epub 2004 Mar 17.
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.
单核细胞失活已被确定为脓毒症免疫抑制的主要因素，且与循环单核细胞表面人类白细胞抗原-DR（HLA-DR）表达缺失有关。我们使用流式细胞术、定量逆转录-聚合酶链反应，对脓毒症患者的这一现象进行了研究。我们证实了所有感染患者单核细胞HLA-DR表达早期缺失，并表明第6天这种持续降低的表达与严重程度评分、继发感染及死亡相关。这一现象通过II类反式激活因子A（CIITA）转录减少在转录水平发生。此外，这些异常与脓毒症中观察到的高皮质醇水平相关，而与儿茶酚胺或白细胞介素-10等其他假定因素无关。最后，体外研究证明糖皮质激素通过降低CIITA mRNA水平，主要是下调其I型和III型异构体，在转录水平降低HLA-DR表达。我们得出结论，在人类脓毒症中，循环单核细胞上HLA-DR表达缺失与不良预后相关。我们认为脓毒性休克中观察到的高内源性皮质醇水平可能是通过其对HLA-DR和CIITA转录的影响，参与单核细胞HLA-DR表达缺失的一个可能新因素。
