Although the extracellular release of HMGB1 has been reported by several investigators in patients with infection and sepsis, only one study has described HMGB1 release in plasma in a small group of patients several hours after trauma [17]. It has been shown that HMGB1 is released early in the plasma of animals that undergo hemorrhagic shock and trauma and functions as one selleck chemicals of the key mediators of the sterile inflammation induced by ischemia-reperfusion injury [18]. However, it is not known whether HMGB1 is also released in the plasma early after trauma in humans and this open experimental question constitutes the first aim of this study.

Furthermore, because HMGB1 has been shown to induce microvascular thrombosis and endothelial cell activation [19] and because we have previously described an activation of the protein C and of the complement pathways that occurs nearly immediately after trauma [9,20], we also sought to define the relations between plasma levels of HMGB1, activation of coagulation and of the protein C system and the release of other markers of inflammation and endothelial activation early after trauma. Here, we report an extracellular release of HMGB1 within 30 minutes after trauma that correlates with severity of injury, tissue hypoperfusion, activation of the protein C system and coagulation abnormalities, complement activation and the release of other biomarkers of endothelial cell activation after severe trauma in humans.

Materials and methodsThe Institutional Review Board of the University of California at San Francisco approved the research protocol for this prospective cohort study and granted a waiver of consent for the blood sampling as it was a minimal risk intervention.PatientsConsecutive major trauma patients admitted to the San Francisco General Hospital (level one trauma center) were studied. All adult trauma patients who met criteria for full trauma team activation were eligible for enrollment. Patients less than 18 years old or transferred from other hospitals were excluded. In addition, patients with previous coagulation abnormalities were also excluded from the study.Sample collection and measurementsThe methodology has been described previously in detail [20]. Briefly, a 10 ml sample of blood was drawn in citrated tubes within 10 minutes of arrival in the emergency department. The samples were immediately transferred to the central laboratory, centrifuged and the plasma extracted and stored at -80��C. Samples were analyzed at the AV-951 conclusion of the study by researchers who were blinded to all patients data. In this study, we measured HMGB1 (HMGB-1 ELISA kit IBL, Transatlantic LLC, Osceola, WI, USA). These results were compared with IL-6, TNF-�� (both from R&D Systems Inc.