End organ dysfunction in trauma and hemorrhagic shock results from systemic inflammatory responses (112) . Barsness et al. provided indirect evidence that HMGB1 may be involved in the pathogenesis of end organ injury following hemorrhagic shock by linking TLR4 activation to the development of acute lung injury (113) . Subsequently, it has been shown that pulmonary HMGB1 levels are increased as early as 4 h after the initiation of hemorrhagic shock (114) . Furthermore, HMGB1 neutralizing antibodies ameliorate hemorrhage-induced acute lung injury (114) as well as gut barrier dysfunction and ultimately lead to improved survival (115) . These findings are even more relevant given the clinical observation that circulating HMGB1 levels are elevated in trauma patients with hemorrhagic shock as compared with normal volunteers (115) .