Sepsis-induced Innate and Adaptive Immune Suppression

The inflammatory response to sepsis has classically been characterized by an overactive innate immune response. Recent adult and pediatric evidence suggests that the immune response is quite dynamic in this setting, often with endogenous innate and adaptive immunosuppression following the onset of sepsis. Sepsis-induced innate immune dysfunction can include reduction in antigen presenting capacity (as evidenced by decreased monocyte HLA-DR expression) and low pro-inflammatory cytokine production capacity (as evidenced by reduced ex vivo LPS-induced tumor necrosis factorproduction). The term immunoparalysis describes a state of severe reduction in these parameters and has been associated with increased risks for the development of nosocomial infection and death in septic adults and children. Intriguing evidence suggests that immunoparalysis may be reversible with beneficial effects on outcomes. Adaptive immune dysfunction has also been reported following the onset of sepsis. Lymphopenia, lymphocyte apoptosis, and skewing toward anti-inflammatory T cell subtypes (such as regulatory T cells) have all been associated with adverse outcomes from sepsis. Without specific testing, most aspects of sepsis-related immune dysfunction are occult. Accordingly, the development of robust immune monitoring and modulation protocols should be a high priority in the battle to improve outcomes from sepsis in critically ill adults and children.