• Matthias Majetschak, Stephen M Cohn, Udo Obertacke, and Kenneth G Proctor.
• Daughtry Department of Surgery, Divisions of Trauma and Surgical Critical Care, Ryder Trauma Center, University of Miami School of Medicine, Miami, Florida, USA. mmajetschak@med.miami.edu
• J Trauma. 2004 May 1; 56 (5): 991-9; discussion 999-1000.

BackgroundRecent studies suggest that extracellular ubiquitin could have a physiologic role in immunodepression in sepsis and trauma. The therapeutic potential of exogenous ubiquitin after trauma has not been examined. To fill this gap, we designed a series of experiments in a clinically relevant trauma model.MethodsForty minutes after femur fractures and hemorrhage, swine received 1.3 mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor necrosis factor-alpha (TNF alpha) production ex vivo. TNF alpha and ubiquitin were quantified with enzyme-linked immunosorbent assay.ResultsIntravenous ubiquitin had no significant hemodynamic effect in normal animals. After injury, ubiquitin significantly reduced fluid requirements by at least 60% (p < 0.05). The injury was associated with transient immunodepression, as reflected by reduced endotoxin-evoked TNF alpha production by 40% to 50%. With ubiquitin, this response remained depressed for 100 to 160 minutes (p < 0.05), but fully recovered to baseline with albumin.ConclusionUbiquitin is apparently safe and effective for reducing fluid requirements as a measure of diffuse capillary leak. This immunomodulatory property suggests a new therapeutic approach after injury in particular, and for infectious and noninfectious inflammation in general.

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