Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients

程序性死亡-1 水平与脓毒症休克患者死亡率增加、院内感染和免疫功能障碍相关

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作者:Caroline Guignant, Alain Lepape, Xin Huang, Hakim Kherouf, Laure Denis, Françoise Poitevin, Christophe Malcus, Aurélie Chéron, Bernard Allaouchiche, François Gueyffier, Alfred Ayala, Guillaume Monneret, Fabienne Venet

Conclusions

These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.

Methods

This prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed.

Results

We observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration. Conclusions: These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.

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