title: Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study.
abstract: Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients.
  
  
  
  A single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1-2, days 3-4, and days 6-8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection.
  
  
  
  Twenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3-4 (p = 0.04) and days 6-8 (p = 0.002). The change in HLA-DR from days 1-2 to days 6-8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1-2 to days 3-4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection.
  
  
  
  Monocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO, USA. drewrya@anest.wustl.edu.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Drewry
authors.affiliation: Departments of Anesthesiology and Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Enyo A
authors.initials: EA
authors.lastname: Ablordeppey
authors.affiliation: University of Missouri-Columbia School of Medicine, Columbia, MO, USA.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Murray
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO, USA.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Beiter
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Walton
authors.affiliation: Department of Pediatrics, Critical Care Medicine, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hall
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016638:Critical Illness / Q000453:epidemiology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D008923:Missouri / Q000453:epidemiology; D063868:Patient Outcome Assessment; D011379:Prognosis; D011446:Prospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000401:mortality*; D018709:Statistics, Nonparametric; D017741:Survivors / Q000706:statistics & numerical data; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha
keywords: Immunosuppression; Monocytes; Mortality; Sepsis