Serial increase of IL-12 response and human leukocyte antigen-DR expression in severe sepsis survivors

Abstract

Introduction: Sepsis-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. Methods: We 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. Results: Of 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. Conclusions: Monocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis.