Sepsis, a systemic inflammatory response to
infection, is a leading cause of death in intensive care units. Recent investigations into the pathogenesis of
sepsis reveal a biphasic inflammatory process. An early phase is characterized by pro-inflammatory
cytokines (e.g. tumour
necrosis factor-alpha), whereas a late phase is mediated by an inflammatory high-mobility group box 1 and an anti-inflammatory
interleukin-10.
Inflammation aberrantly activates coagulation cascades as
sepsis progresses. This dual inflammatory response concomitant with dysregulated coagulation partially accounts for unsuccessful anti-
cytokine therapies that have solely targeted early pro-inflammatory mediators (e.g. tumour
necrosis factor-alpha). In contrast, activated
protein C, which modifies both inflammatory and coagulatory pathways, has improved survival in patients in
severe sepsis. Inhibition of the late mediator high-mobility group box 1 improves survival in established
sepsis in pre-clinical studies. In addition, recent advances in molecular medicine have shed light on two novel experimental interventions against
sepsis. Accelerated apoptosis of lymphocytes has been shown to play an important role in organ dysfunction in
sepsis and techniques to suppress apoptosis have improved survival rate in
sepsis models. The vagus nerve system has also been shown to suppress innate immune response through endogenous release and exogenous administration of
cholinergic agonists, ameliorating
inflammation and lethality in
sepsis models.