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
BackgroundIdentifying 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 a) production, to predict mortality and morbidity. The purpose of this study was to compare HLA DR expression and LPS induced TNF a production as predictors of 28 day mortality and acquisition of secondary infections in adult septic patients.MethodsA 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 a 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.ResultsTwenty 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 a production did not differ between survivors and non survivors or between patients who did and did not develop a secondary infection.ConclusionsMonocyte HLA DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS stimulated TNF a production in adult medical and surgical critically ill patients.
Critical Care