Blood samples were obtained from 168 consecutive major trauma pat

Blood samples were obtained from 168 consecutive major trauma patients selleck bio immediately upon admission to the hospital. (a) Trauma patients with coagulation abnormalities …Figure 4High plasma levels of HMGB1 are associated with increased fibrinolytic activity in trauma patients. Blood samples were obtained from 168 consecutive major trauma patients immediately upon admission to the hospital. (a to c) High plasma levels of high …Plasma levels of HMGB1 and clinical outcome in trauma patientsFinally, to determine the clinical significance of these findings, we examined whether HMGB1 release into the bloodstream within 30 minutes after injury was associated with worse clinical outcome. We found that there was a direct relation between mortality rate and plasma levels of HMGB1.

A doubling of HMGB1 levels was associated with a 1.7 times likelihood of death (odds ratio 1.70; 95% confidence interval 1.12 to 2.60; P = 0.01; Figures Figures5a5a to to5b).5b). Non-survivors (n = 26) had significantly higher than plasma levels of HMGB1 than survivors (n = 183; Figures Figures5a5a and and5b).5b). Furthermore, patients who later developed organ injury, such as acute lung injury (n = 18) and acute renal failure (n = 23). had also significantly higher plasma levels of HMGB1 measured immediately after admission to the Emergency Department within 45 minutes after injury (Figure (Figure5c5c).Figure 5High plasma levels of HMGB1 are associated with increased mortality and end-organ injury in trauma patients. (a) Baseline plasma levels of high mobility group box nuclear protein 1 (HMGB1) after severe trauma were higher in non-survivors compared with .

..DiscussionThe results of this study demonstrate for the first time that: (a) HMGB1, a known early mediator of sterile inflammation, is released in the plasma within 45 minutes after severe trauma in humans; (b) the release of HMGB1 in the plasma requires severe tissue injury and tissue hypoperfusion; and (c) HMGB1 is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.Severe trauma is associated with an early SIRS seen within 30 to 60 minutes after injury followed by a CARS observed 24 to 48 hours after injury, although the molecular mechanisms responsible for this altered host defense are not well understood [2-4].

Recent studies have provided new information on the molecular mechanisms that lead to the early inflammatory response. Complement and alarmins have been shown in experimental studies to play an important role as endogenous triggers of trauma-associated inflammation. Among the alarmins, HMGB1 appears to be one of the important mediators in triggering Carfilzomib this posttraumatic sterile inflammation via receptors, such as TLR4 and RAGE [12-14,29] (Figure (Figure6).6). However, whether HMGB1 is an early mediator of the early inflammatory response induced by severe trauma in humans is unknown.

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