Biphasic release of the alarmin high mobility group box 1 protein early after trauma predicts poor clinical outcome

Abstract

<i>Objective</i>: The causal role of the prototype alarmin high mobility group box 1 protein (HMGB1) in systemic inflammation and remote organ injury after trauma and shock is established in animal models but not in humans. Our aim was therefore to determine HMGB1 concentration kinetics with high time resolution during the first hours after trauma in individual patients, and investigate the association with outcome.<p>

<p><i>Design</i>: Prospective single-center observational study.<p>

<p><i>Setting</i>: University hospital Level I trauma center.<p>

<p><i>Patients</i>: Convenience recruitment of 136 trauma patients.<p>

<p><i>Interventions</i>: None.<p>

<p><i>Measurements and Main Results</i>: Total plasma HMGB1 levels were analyzed with ELISA in repeated samples. Relationships between predefined predictor variables and outcome were examined in multivariable linear regression models. Ventilator-free days was used as primary outcome measure. Two distinct HMGB1 release phases were identified. An initial exponential decay phase with a half-life of 26 min was not correlated with outcome. In contrast, a second HMGB1 wave peaking 3–6 hours after trauma in the most severely injured and physiologically deranged patients was strongly correlated with outcome.<p>

<p><i>Conclusions</i>: HMGB1 was released in two consecutive phases. Only the second HMGB1 wave was a significant predictor of outcome. Patients with a high HMGB1 concentration between 3 and 6 hours after trauma might benefit from HMGB1-specific antagonist therapy.