Abstract

High-mobility group box 1 (HMGB1) is a late mediator of the systemic inflammation associated with sepsis. Recently, HMGB1 has been shown in animals to be a mediator of hemorrhage-induced organ dysfunction. However, the time course of plasma HMGB1 elevations following trauma in humans remains to be elucidated. Consequently, we hypothesized that mechanical trauma in humans would result in early, significant elevations of plasma HMGB1.

METHODS:

Trauma patients at risk for MOF (ISS >/= 15) were identified for inclusion (n=23) and post-injury plasma samples were assayed for HMGB1 by ELISA. Comparison of post-injury HMGB1 levels with markers for patient outcome (age, injury severity score, units of red blood cell (RBC) transfused/1ST 24 hours, and base deficit) was performed. To investigate whether post-injury transfusion contributes to elevations of circulating HMGB1, levels were determined in both leukoreduced (LR) and non-leukoreduced (NLR) packed RBCs.

RESULTS:

Plasma HMGB1 was elevated >30 fold above healthy controls within one hour of injury (median 57.76ng/ml vs 1.77ng/ml, p<0.003), peaked from 2-6 hours post-injury (median 526.18ng/ml, p<0.01 vs control), and remained elevated above control through 136 hours. No clear relationship was evident between post-injury HMGB1 levels and markers for patient outcome. HMGB1 levels increase with duration of RBC storage, though concentrations did not account for post-injury plasma levels. LR attenuated HMGB1 levels in packed RBCs by approximately 55% (p<0.01).

CONCLUSION:

Plasma HMGB1 is significantly increased within one hour of trauma in humans with marked elevations occurring from 2-6 hours post-injury. These results suggest that, in contrast to sepsis, HMGB1 release is an early event following traumatic injury in humans. Thus, HMGB1 may be integral to the early inflammatory response to trauma and is a potential target for future therapeutics.