Abstract
Sepsis is the leading cause of mortality in intensive care units due to complex inflammatory immune responses and immunosuppression. Recent studies have indicated that the negative regulator of toll like receptors, interleukin-1 receptor-associated kinase 3 (IRAK-3/IRAK-M), serves an important role in immunosuppression during sepsis. In the current study, a cecal ligation puncture model was established in mice using lipopolysaccharide secondary challenge to simulate immunosuppression in sepsis. Peripheral blood mononuclear cells (PBMCs) from this model were then used to evaluate the expression and function of IRAK-M. The results demonstrated that silencing of IRAK-M expression in PBMCs from immunosuppressed mice partially restored the production of pro-inflammatory cytokines. By introducing PBMCs transfected with small-interfering RNA targeting IRAK-M into septic immunosuppressed mice, the survival rate was improved with an increase in splenic CD4+ and CD8+ T cells and a decrease in T cell apoptosis. In conclusion, downregulation of IRAK-M reversed the effects of sepsis on the production of inflammatory cytokines in PBMCs, and improved the survival of septic immunosuppressed mice. These results provide a basis for future studies investigating the immunological mechanisms underlying immune suppression in sepsis.