Therapeutic Potential of Exogenous Ubiquitin during Resuscitation from Severe Trauma

Abstract

Ubiquitin 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.

Chemokine (C-X-C Motif) Receptor 4 and Atypical Chemokine Receptor 3 Regulate Vascular α1-Adrenergic Receptor Function

“…In combination with previously described effects of ubiquitin in various shock models (19)(20)(21)45), these data indicate that selective CXCR4 activation stabilizes blood pressure during the cardiovascular stress response to hemorrhagic shock, providing an extended therapeutic window during which blood pressure can be restored with fluid resuscitation.…”

“…As expected (19,21,(45)(46)(47) Next, we studied the effects of the CXCR4 and ACKR3 ligands that did not influence normal blood pressure in a hemorrhagic shock model. This model consisted of 30 min hemorrhage to a mean arterial blood pressure (MAP) of 30 mmHg followed by crystalloid fluid resuscitation to a MAP of 70 mmHg.…”

Systemic Ubiquitin Release After Blunt Trauma and Burns: Association With Injury Severity, Posttraumatic Complications, and Survival

“…Ub inhibited the LPS evoked tumor necrosis factor-␣ and interleukin-8 responses of whole blood and peripheral blood mononuclear cells in vitro and in vivo 13,14,18 and also enhanced the anti-inflammatory Th2 tissue cytokine response during inflammation in vivo. 22 These immunologic effects were accompanied by a significant reduction of third spacing of fluids in models of endotoxic shock, traumatic shock, and lung ischemia-reperfusion injury.…”

Initial Assessment of the Role of CXC Chemokine Receptor 4 after Polytrauma

“…Although the regulation of SDF-1α levels after trauma and its association with clinical outcomes are largely unknown, administration of SDF-1α and of various SDF-1α mimetic proteins have been shown to result in beneficial effects in models of acute infectious and sterile inflammation in vivo (18)(19)(20)(21)(22). Similarly, treatment with exogenous ubiquitin has been shown to attenuate inflammation and to confer organ protection in animal models, including various models of trauma and hemorrhage (23)(24)(25)(26)(27)(28)(29)(30). Collectively, these studies imply CXCR4 as a promising drug target for trauma patients and suggest that CXCR4 may play an important role during the inflammatory response to tissue injury.…”