title: Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma.
abstract: OBJECTIVE
  To determine whether treatment with the CXC chemokine receptor 4 agonist ubiquitin results in beneficial effects in a polytrauma model consisting of bilateral femur fractures plus blunt chest trauma (Injury Severity Score 18-25).
  
  
  METHODS
  Treatment study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Seventeen Yorkshire pigs.
  
  
  METHODS
  Intravenous injection of 1.5 mg/kg ubiquitin or albumin (control) at 60 mins after polytrauma.
  
  
  RESULTS
  Anesthetized, mechanically ventilated pigs underwent polytrauma, followed by a simulated 60-min shock phase. At the end of the shock phase, ubiquitin or albumin were administered and animals were resuscitated to a mean arterial blood pressure of 70 mm Hg until t=420 mins. After intravenous ubiquitin, ubiquitin plasma concentrations increased 16-fold to 2870±1015 ng/mL at t=90 mins and decreased with t1/2=60 mins. Endogenous plasma ubiquitin increased two-fold in the albumin group with peak levels of 359±210 ng/mL. Plasma levels of the cognate CXC chemokine receptor 4 ligand stromal cell-derived factor-1α were unchanged in both groups. Ubiquitin treatment reduced arterial lactate levels and prevented a continuous decrease in arterial oxygenation, which occurred in the albumin group during resuscitation. Wet weight to dry weight ratios of the lung contralateral from the injury, heart, spleen and jejunum were lower with ubiquitin. With ubiquitin treatment, tissue levels of Interleukin-8, Interleukin-10, Tumor Necrosis Factor α, and stromal cell-derived factor-1α were reduced in the injured lung and of Interleukin-8 in the contralateral lung, respectively.
  
  
  CONCLUSIONS
  Administration of exogenous ubiquitin modulates the local inflammatory response, improves resuscitation, reduces fluid shifts into tissues, and preserves arterial oxygenation after blunt polytrauma with lung injury. This study further supports the notion that ubiquitin is a promising protein therapeutic and implies CXC chemokine receptor 4 as a drug target after polytrauma.
authors.affiliation: Burn and Shock Trauma Institute-Department of Surgery, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Baker
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Romero
authors.forename: Harold H
authors.initials: HH
authors.lastname: Bach
authors.forename: Joel A
authors.initials: JA
authors.lastname: Strom
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Matthias
authors.initials: M
authors.lastname: Majetschak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005264:Femoral Fractures / Q000150:complications / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009104:Multiple Trauma / Q000150:complications / Q000188:drug therapy*; D019718:Receptors, CXCR4 / Q000819:agonists*; D013552:Swine; D013898:Thoracic Injuries / Q000150:complications / Q000188:drug therapy*; D025801:Ubiquitin / Q000097:blood / Q000627:therapeutic use*; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000188:drug therapy*
chemical_list: D019718:Receptors, CXCR4; D025801:Ubiquitin