epoetin-alfa and Burns

Erythropoietin (EPO) is an endogenous regulator of erythropoiesis and is given exogenously as a replacement therapy for selected red blood cell disorders. In the past years, EPO has been emerging as a multifunctional, cytoprotective cytokine with anti-apoptotic, anti-inflammatory, and immunomodulatory properties. We aimed to evaluate the cytoprotective effect of rhEPO (recombinant human EPO) treatment on a rat model of multiorgan dysfunction induced by thermal injury. rhEPO was administered at 1000 U/kg (i.v.) 5 min prior to induction of injury and significantly reduced multiorgan dysfunction markers (liver, kidney, lung, serum cytokine levels). In the lung, rhEPO reduced: histological signs of tissue injury, inflammatory/injury markers on the bronchoalveolar fluid, neutrophil chemotaxis/infiltration, GSK-3β activation, and apoptosis. Our study showed that erythropoietin has the potential to exhibit pleiotropic cytoprotective effects and that it might be an interesting pharmacological strategy in the modulation of acute lung injury, such as the one associated to severe burn.

Topics: Acute Lung Injury; Animals; Burns; Dose-Response Relationship, Drug; Epoetin Alfa; Humans; Inflammation; Male; Multiple Organ Failure; Neutrophils; Rats; Rats, Wistar; Recombinant Proteins; Respiratory Burst

Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

Topics: Animals; Brain Injuries; Burns; Epoetin Alfa; Erythropoietin; Gene Expression Regulation; Humans; Mice; Models, Theoretical; Neovascularization, Physiologic; Recombinant Proteins; Vascular Endothelial Growth Factor A; Wound Healing