title: HMGB1 is markedly elevated within 6 hours of mechanical trauma in humans.
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 after trauma in humans remains to be elucidated. Consequently, we hypothesized that mechanical trauma in humans would result in early significant elevations of plasma HMGB1. Trauma patients at risk for multiple organ failure (ISS > or = 15) were identified for inclusion (n = 23), and postinjury plasma samples were assayed for HMGB1 by enzyme-linked immunosorbent assay. Comparison of postinjury HMGB1 levels with markers for patient outcome (age, injury severity score, units of red blood cell (RBC) transfused per first 24 h, and base deficit) was performed. To investigate whether postinjury transfusion contributes to elevations of circulating HMGB1, levels were determined in both leuko-reduced and non-leuko-reduced packed RBCs. Plasma HMGB1 was elevated more than 30-fold above healthy controls within 1 h of injury (median, 57.76 vs. 1.77 ng/mL; P < 0.003), peaked from 2 to 6 h postinjury (median, 526.18 ng/mL; P < 0.01 vs. control), and remained elevated above control through 136 h. No clear relationship was evident between postinjury HMGB1 levels and markers for patient outcome. High-mobility group box 1 levels increase with duration of RBC storage, although concentrations did not account for postinjury plasma levels. Leuko-reduced attenuated HMGB1 levels in packed RBCs by approximately 55% (P < 0.01). Plasma HMGB1 is significantly increased within 1 h of trauma in humans with marked elevations occurring from 2 to 6 h postinjury. These results suggest that, in contrast to sepsis, HMGB1 release is an early event after traumatic injury in humans. Thus, HMGB1 may be integral to the early inflammatory response to trauma and is a potential target for future therapeutics.
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Erik D
authors.initials: ED
authors.lastname: Peltz
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Eckels
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Damle
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuruta
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Angela
authors.initials: A
authors.lastname: Sauaia
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003422:Critical Care; D017707:Erythrocyte Transfusion; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood; D012720:Severity of Illness Index; D012769:Shock / Q000097:blood; D014947:Wounds and Injuries / Q000097:blood*; D055815:Young Adult
chemical_list: D024243:HMGB1 Protein