title: Phenotype and functions of natural killer cells in critically-ill septic patients.
abstract: BACKGROUND
  Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models.
  
  
  OBJECTIVE
  We studied the phenotype and functions of circulating NK cells in critically-ill septic patients.
  
  
  METHODS
  Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry.
  
  
  RESULTS
  The absolute number of peripheral blood CD3-CD56(+) NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3-70]%) compared to healthy controls (43.5[32.1-53.1]%) or Sepsis patients (49.2[37.3-62.9]%) (p = 0.002). Compared to healthy (10.2[6.3-13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2-9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1-54.7]%) compared to Sepsis patients (18.4[11.7-35.7]%, p<0.01) or healthy controls (26.8[19.3-44.9]%, p = 0.09) in ADCC condition.
  
  
  CONCLUSIONS
  Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions.
  
  
  BACKGROUND
  NTC00699868.
authors.affiliation: Faculté de médecine, Aix-Marseille Université, URMITE UMR CNRS 7278, Marseille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Forel
authors.forename: Laurent
authors.initials: L
authors.lastname: Chiche
authors.forename: Guillemette
authors.initials: G
authors.lastname: Thomas
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.forename: Catherine
authors.initials: C
authors.lastname: Farnarier
authors.forename: Céline
authors.initials: C
authors.lastname: Cognet
authors.forename: Christophe
authors.initials: C
authors.lastname: Guervilly
authors.forename: Aurélie
authors.initials: A
authors.lastname: Daumas
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vély
authors.forename: François
authors.initials: F
authors.lastname: Xéridat
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
mesh_terms: D000368:Aged; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000401:mortality; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000276:immunology* / Q000401:mortality
chemical_list: D016207:Cytokines