title: Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients.
abstract: BACKGROUND
  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.
authors.affiliation: Hospices Civils de Lyon, Hôpital E, Herriot, Laboratoire d'Immunologie, 5 Place d'Arsonval, 69003 Lyon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Guignant
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Hakim
authors.initials: H
authors.lastname: Kherouf
authors.forename: Laure
authors.initials: L
authors.lastname: Denis
authors.forename: Françoise
authors.initials: F
authors.lastname: Poitevin
authors.forename: Christophe
authors.initials: C
authors.lastname: Malcus
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chéron
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
mesh_terms: D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D003428:Cross Infection / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008934:Mitogens; D009000:Monocytes / Q000378:metabolism; D011446:Prospective Studies; D012772:Shock, Septic / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D008934:Mitogens; D016753:Interleukin-10