• Jean-Marie Forel, Laurent Chiche, Guillemette Thomas, Julien Mancini, Catherine Farnarier, Céline Cognet, Christophe Guervilly, Aurélie Daumas, Frédéric Vély, François Xéridat, Eric Vivier, and Laurent Papazian.
• Faculté de médecine, Aix-Marseille Université, URMITE UMR CNRS 7278, Marseille, France.
• Plos One. 2012 Jan 1;7(12):e50446.

RationaleNatural 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.ObjectiveWe studied the phenotype and functions of circulating NK cells in critically-ill septic patients.MethodsBlood 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.ResultsThe 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.ConclusionsExtensive 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.Trial RegistrationNTC00699868.

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