Sepsis, the 10th leading cause of death, is the most expensive condition in the United States. The immune response in sepsis transitions from hyperinflammatory to a hypoinflammatory and immunosuppressive phase; individual variations regarding timing and overlap between hyper- and hypoinflammation exist in a number of patients. While one third of the sepsis-related deaths occur during hyperinflammation, majority of the sepsis-mortality occurs during the hypoinflammatory phase. Currently, no phase-specific molecular-based therapies exist to treat sepsis. Coordinated epigenetic and metabolic perturbations orchestrate this shift from hyper- to hypoinflammation in innate immune cells during sepsis. These epigenetic and metabolic changes during sepsis progression and therapeutic opportunities they pose are described in this review.
Keywords: Epigenetic programming; hyperinflammation; hypoinflammation; immunosuppression; metabolism; sepsis; septic shock.