The new normal: immuno-modulatory agents against sepsis immune suppression

Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as IL-7, IL-15, GM-CSF as well as co-inhibitory molecule blockade, such as anti-PD-1 and anti-BTLA, may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics.