title: Innate Immune Function and Organ Failure Recovery in Adults With Sepsis.
abstract: OBJECTIVE
  Sepsis stimulates pro- and anti-inflammatory immune responses. The innate immune response is critical to organ injury repair. We tested for an association between innate immune function and organ function recovery in a prospective cohort of immune-competent adults with sepsis.
  
  
  METHODS
  We conducted a prospective observational cohort study enrolling immune-competent adults with sepsis. We tested innate immune function by quantification of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production capacity in whole blood samples on hospital days 1, 4, and 6. The primary outcome was organ function recovery on day 4 defined as a 4-point decrease in the composite cardiovascular and respiratory Sequential Organ Failure Assessment (SOFA) score components or a SOFA score ≤2.
  
  
  RESULTS
  Patients with sepsis who recovered organ function by day 4 (n = 11) had similar baseline characteristics when compared to those with ongoing organ failure (n = 13). Tumor necrosis factor α production capacity was similar between the 2 groups on hospital days 1 and 4 but significantly different on day 6. Patients who regained organ function recovery had significantly higher TNF-α production capacity on day 6 ( P = .01), which persisted after adjustment for age, Acute Physiology and Chronic Health Evaluation III score, and steroid administration ( P = .03). There was no difference in TNF-α production capacity over time in those who survived to hospital discharge versus nonsurvivors.
  
  
  CONCLUSIONS
  Increasing TNF-α production capacity is associated with improved organ failure recovery. Further studies are needed to evaluate a causal association between innate immune suppression and organ failure recovery as well as predictive accuracy for hospital survival. Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery.
authors.affiliation: 1 Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine, Aurora, CO, USA.|2 Children's Hospital Colorado, Aurora, CO, USA.
authors.forename: Aline B
authors.initials: AB
authors.lastname: Maddux
authors.affiliation: 3 Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, Denver Health Medical Center, Denver, CO, USA.
authors.forename: Terra D
authors.initials: TD
authors.lastname: Hiller
authors.affiliation: 3 Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, Denver Health Medical Center, Denver, CO, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Overdier
authors.affiliation: 1 Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine, Aurora, CO, USA.|4 Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Pyle
authors.affiliation: 1 Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine, Aurora, CO, USA.|3 Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, Denver Health Medical Center, Denver, CO, USA.
authors.forename: Ivor S
authors.initials: IS
authors.lastname: Douglas
mesh_terms: D015415:Biomarkers / Q000097:blood; D003422:Critical Care; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology; D007362:Intensive Care Units; D018655:Lymphocyte Count; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy
chemical_list: D015415:Biomarkers
keywords: critical care; endotoxin tolerance; immune tolerance; innate immunity; multiple organ failure