• Céline Pangault, Yves Le Tulzo, Pierre Tattevin, Valérie Guilloux, Nadège Bescher, and Bernard Drénou.
• Département d'Hématologie, Immunologie et Thérapie Cellulaire, Hôpital Pontchaillou, Centre Hospitalier Universitaire, Rennes, France. celine.pangault@univ-rennes1.fr
• Crit. Care Med. 2006 Apr 1;34(4):1193-201.

ObjectiveLoss of surface human leukocyte antigen-DR (HLA-DR) on monocytes is a major factor of immunosuppression in sepsis. Granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulates HLA-DR expression on monocytes via the GM-CSF receptor (GM-CSFr) through a transcriptional mechanism involving the class II transactivator factor (CIITA). We investigated monocyte GM-CSFr expression and its relationship with HLA-DR in septic patients.DesignProspective clinical experimental study.SettingUniversity hospital intensive care unit and research facility.PatientsSeptic patients with and without septic shock, control patients.InterventionsFlow cytometry and real-time quantitative reverse polymerase chain reaction were used to characterize GM-CSFr expression and transcription in septic patients and in ex vivo stimulated healthy monocytes.Measurements And Main ResultsWe showed an early GM-CSFr down-modulation in patients with septic shock compared with those without septic shock and controls. A persistent low GM-CSFr expression was observed in patients who acquired secondary infections or in those who died, and this persistent defect correlated with severity scores. We demonstrated that GM-CSFr down-modulation occurs at a posttranscriptional level since we observed no alteration in GM-CSFr transcription in monocytes isolated from septic patients. Furthermore, we demonstrated that GM-CSFr expression levels on monocytes correlated not only with HLA-DR expression and transcription levels but also with RNA levels of its main transcriptional factor CIITA. Because we previously showed in septic patients a relationship between high cortisol plasma level and low monocyte HLA-DR expression, we investigated the effects of glucocorticoids on monocyte GM-CSFr expression and observed a similar posttranscriptional down-modulation of GM-CSFr by steroids. However, the in vivo putative role of steroids in HLA-DR down-regulation via GM-CSFr down-modulation needs further investigation.ConclusionMonocyte GM-CSFr down-modulation occurred in septic shock, was associated with severity, and might be either another manifestation of monocyte deactivation linked to sepsis or an additional mechanism participating in immunosuppression.

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