Open Access Research

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

Caroline Guignant1, Alain Lepape2, Xin Huang3, Hakim Kherouf1, Laure Denis4, Françoise Poitevin1, Christophe Malcus1, Aurélie Chéron5, Bernard Allaouchiche5, François Gueyffier6, Alfred Ayala3, Guillaume Monneret1* and Fabienne Venet1

Author Affiliations

1 Hospices Civils de Lyon, Hôpital E. Herriot, Laboratoire d'Immunologie, 5 Place d'Arsonval, 69003 Lyon, France

2 Hospices Civils de Lyon, CH Lyon-Sud, Service de Réanimation, Chemin du Grand Revoyet, 69495 Pierre-Bénite, France

3 Division of Surgical Research, Department of Surgery, Brown University School of Medicine/Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA

4 Hospices Civils de Lyon, CH Lyon-Sud, Laboratoire d'Immunologie, Chemin du Grand Revoyet, 69495 Pierre-Bénite, France

5 Hospices Civils de Lyon, Hôpital E. Herriot, Service de Réanimation, 5 Place d'Arsonval, 69003 Lyon, France

6 Hospices Civils de Lyon/INSERM, Centre d'Investigation Clinique (CIC 0201), 52, Boulevard Pinel, 69003 Lyon, France

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Critical Care 2011, 15:R99  doi:10.1186/cc10112

Published: 21 March 2011

Abstract

Introduction

Septic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients.

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.