• Vidula Vachharajani, Tiefu Liu, and Charles E McCall.
• Department of Anesthesiology, Section on Critical Care, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.
• Expert Rev Clin Immunol. 2014 Sep 1; 10 (9): 1141-50.

AbstractEpigenetic reprogramming of thousands of genes directs the course of acute systemic inflammation, which is highly lethal when dysregulated during sepsis. No molecular-based treatments for sepsis are available. A new concept supports that sepsis is an immunometabolic disease and that loss of control of nuclear epigenetic regulator sirtuin 1 (SIRT-1), a NAD(+) sensor directs immune and metabolic pathways during sepsis. SIRT-1, acting as homeostasis checkpoint, controls hyper- and hypo-inflammatory responses of sepsis at the microvascular interface, which disseminates inflammatory injury to cause multiple organ failure. Modifying SIRT-1 activity, which can prevent or treat established sepsis in mice, may provide a new way to treat sepsis by epigenetically restoring immunometabolic homeostasis.

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