Abstract
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-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.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-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.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-ɑ 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-ɑ production in adult medical and surgical critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users.
Highlights
Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies
There were no significant differences between the two groups in terms of age, gender, source of sepsis, proportion of patients with positive cultures, or type of infecting organism
Leukocyte counts in each group for the first 7 days after sepsis diagnosis are shown in Additional file 3
Summary
Identifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Sepsis-induced immunosuppression is a term used to describe the immunosuppressive phenotype that develops in many patients with protracted sepsis It is characterized by numerous abnormalities in the innate and adaptive immune systems including increased immune cell apoptosis, impaired phagocytosis, diminished antigen-presenting ability, and dysregulated cytokine production [1]. Septic patients with these abnormalities are less able to eliminate primary infections and are more susceptible to secondary nosocomial infections, including those caused by opportunistic organisms [2]. Greater appreciation for the role of immune dysfunction in sepsis mortality has led to clinical trials of immunomodulatory agents that stimulate the immune system. Other potential immunotherapy agents, such as anti-programmed cell death ligand 1 (PD-L1) antibody and interleukin 7 (IL-7), have shown benefit in animal models of sepsis and are currently being tested in clinical trials [6, 7]
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