Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis.

Surgical injury can be a life-threatening complication, not only due to the injury itself, but also due to immune responses to the injury and subsequent development of infections, which readily result in sepsis. Sepsis remains the leading cause of death in most intensive care units. Unfavorable outcomes of several high-profile trials in the treatment of sepsis have led researchers to state that sepsis studies need a new direction. The immune response that occurs during sepsis is characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immunosuppressive phase. Therefore, therapies that improve host immunity might increase the survival of patients with sepsis. Many mechanisms are responsible for sepsis-induced immunosuppression, including apoptosis of immune cells, increased regulatory T cells and expression of programmed cell death 1 on CD4 T cells, and cellular exhaustion. Immunomodulatory molecules that were recently identified include interleukin-7, interleukin-15, and anti-programmed cell death 1. Recent studies suggest that immunoadjuvant therapy is the next major advance in sepsis treatment.