Abstract
IntroductionSepsis-induced immunosuppression may result in death. The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased anti-inflammatory cytokine expression and decreased expression of proinflammatory cytokines. In this study, we sought to determine the mechanisms of immune suppression in severe sepsis by repeated detection.MethodsWe designed this prospective observational study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with severe sepsis.ResultsOf the 35 enrolled patients, 23 survived for 28 days and 12 died, 6 of whom died within 7 days. Plasma levels of IL-1β, IL-6, IL-10, IL-17, transforming growth factor (TGF)-β1 and TNF-α were higher, but plasma IL-12 level was lower in septic patients than those in controls. Day 1 plasma levels of IL-1β, IL-6, IL-10 and TGF-β1 in nonsurvivors were higher than those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in survivors. IL-1β response was higher, but IL-12 and TNF-α responses were lower in septic patients than in controls. Day 1 IL-6 response was lower, but day 1 TGF-β1 response was higher in nonsurvivors than in survivors. Plasma IL-6 and IL-10 levels were decreased in survivors after 6 days. IL-6 response was decreased in survivors after 6 days, but IL-12 response was increased. Monocyte percentage was higher, but positive HLA-DR percentage in monocytes and mean fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in controls. MFI of HLA-DR was increased in survivors after 6 days.ConclusionsMonocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis.
Highlights
There were no significant differences in age, gender, Acute Physiology and Chronic Health Evaluation (APACHE) Acute Physiology and Chronic Health Evaluation II (II) score, medical history, infection source or initial antibiotic susceptibility between survivors and nonsurvivors
There were no differences in day 1 plasma levels of IL-12, IL-17 and tumor necrosis factor (TNF)-a or in day 7 levels of IL1b, IL-6, IL-12, IL-17, Transforming growth factor (TGF)-b1 and TNF-a between the two groups
Our current study is the first to report serial increases in IL-12 response from peripheral blood mononuclear cell (PBMC) in survivors with severe sepsis. This result is similar to the results reported by Stanilova et al [9], who showed that survivors with severe sepsis produce more IL-12 from LPS-stimulated PBMCs than nonsurvivors
Summary
The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased antiinflammatory cytokine expression and decreased expression of proinflammatory cytokines. The balance between pro- and anti-inflammatory mediators influences the survival rate of septic patients. Immune system failure and sepsis-induced immunosuppression may result in death [1,2]. Transforming growth factor (TGF)-b1 can downregulate T-cell, macrophage and granulocyte responses, whereas increased plasma TGF-b1 level is associated with severe disease and mortality in patients with severe pneumonia [7]. Baseline plasma levels of TGF-b1 are significantly higher in survivors with severe sepsis [8], the correlation of outcome with TGF-b1 production by PBMCs in patients with severe sepsis is lacking
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