title: Interferon-γ production by natural killer cells and cytomegalovirus in critically ill patients.
abstract: OBJECTIVE
  The mechanisms involved in cytomegalovirus reactivation in critically ill patients who were previously immunocompetent are still unknown. The current study was designed to evaluate the possible role of natural killer cells in the reactivation of cytomegalovirus in these patients.
  
  
  METHODS
  Prospective observational.
  
  
  METHODS
  : A medical intensive care unit of a university hospital.
  
  
  METHODS
  Fifty-one subjects, including 15 patients who experienced cytomegalovirus reactivation (cases) during their intensive care unit stay and 15 patients who matched intensive care unit controls, selected from a cohort of consecutive nonimmunocompromised intensive care unit patients, as well as healthy controls.
  
  
  METHODS
  Tests included weekly systematic immunomonitoring and routine screening for cytomegalovirus infection until discharge from the intensive care unit or death. The immunophenotype and functions of natural killer cells were performed by flow cytometry, and serum levels of pro- and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The overall occurrence of cytomegalovirus reactivation in the cohort was 27%. No differences of natural killer cell effector functions were observed at admission between cases and controls. Instead, before cytomegalovirus reactivation, the ability of natural killer cells to secrete interferon-γ was significantly reduced in cases as compared with controls upon stimulation with antibody-coated target cells (p = .029) and with K562 cell stimulation (p = .029). No phenotypic or quantitative differences were observed between cases and controls. Cases exhibited higher levels of interleukin 10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus reactivation.
  
  
  CONCLUSIONS
  Impaired natural killer cell function with reduced interferon-γ secretion precedes the occurrence of cytomegalovirus reactivation among previously immunocompetent critically ill patients.
authors.affiliation: Réanimation-Détresses Respiratoires et Infections Sévères, Assistance Publique Hôpitaux de Marseille, URMITE CNRS-UMR, Université Aix-Marseille II, Marseille, France. laurent.chiche@ap-hm.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Chiche
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Forel
authors.forename: Guillemette
authors.initials: G
authors.lastname: Thomas
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: Christine
authors.initials: C
authors.lastname: Zandotti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vély
authors.forename: Antoine
authors.initials: A
authors.lastname: Roch
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; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014775:Virus Activation
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma