title: Relation of signal in mononuclear cell with endotoxin response and clinical outcome after trauma.
abstract: BACKGROUND
  We investigated the correlation of proinflammatory transcript nuclear factor κB (NF-κB) and antioxidative gene transcript nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in peripheral blood mononuclear cells (PBMCs) with the tumor necrosis factor α (TNF-α) response after endotoxin stimulation and the clinical outcome of severely injured patients.
  
  
  METHODS
  Thirty-two severe blunt trauma patients (injury severity score>16) with systemic inflammatory response syndrome were enrolled. Age- and sex-matched healthy persons were the controls. Patients' blood samples were obtained at 24 and 72 hours after injury. Peripheral blood mononuclear cells were isolated, and measurements for NF-κB p65 translocation, Nrf2 and phosphorylated inhibitory κB-α expressions, and TNF-α levels were assayed after endotoxin stimulation.
  
  
  RESULTS
  In the trauma patients, TNF-α hyporesponse, depressed NF-κB p65 translocation, and phosphorylated inhibitory κB-α expression in PBMCs were found at 24 and 72 hours after injury; the Nrf2 expressions in PBMCs were not significantly different between patients and controls. The TNF-α levels had significant correlation with the NF-κB translocation and the trend of negative correlation with Nrf2 expression. Fifteen patients had critical injury (injury severity score≥25). Patients with critical injury had a lower NF-κB signal and a lower TNF-α response than did the counter group. Twelve patients developed organ failure; their Nrf2 expressions were significantly lower than those of patients without organ failure.
  
  
  CONCLUSIONS
  The endotoxin hyporesponse associated with NF-κB and Nrf2 signal alternations in PBMCs of injured patients develops early after injury. The hyporesponse of PBMCs with a lower TNF-α level correlates with a lower NF-κB signal and is associated with critical injury, whereas a depressed Nrf2 expression in PBMCs is associated with later organ failure in trauma patients.
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University, and Department of Emergency, Taipei Veterans General Hospital, Taipei, Taiwan ROC. hcshih@vghtpe.gov.tw
authors.forename: Hsin-Chin
authors.initials: HC
authors.lastname: Shih
authors.forename: Mu-Shun
authors.initials: MS
authors.lastname: Huang
authors.forename: Chen-Hsen
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000097:blood; D015601:Injury Severity Score; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology; D051267:NF-E2-Related Factor 2 / Q000097:blood*; D016328:NF-kappa B / Q000097:blood*; D011379:Prognosis; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014949:Wounds, Nonpenetrating / Q000097:blood* / Q000150:complications
chemical_list: D015415:Biomarkers; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D014409:Tumor Necrosis Factor-alpha