• Mariarosaria Galeano, Domenica Altavilla, Alessandra Bitto, Letteria Minutoli, Margherita Calò, Patrizia Lo Cascio, Francesca Polito, Giovanni Giugliano, Giovanni Squadrito, Chiara Mioni, Daniela Giuliani, Francesco S Venuti, and Francesco Squadrito.
• Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
• Crit. Care Med. 2006 Apr 1;34(4):1139-46.

ObjectiveErythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds.DesignRandomized experiment.SettingResearch laboratory.SubjectsC57BL/6 male mice weighing 25-30 g.InterventionsMice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 microL subcutaneously) or its vehicle alone (100 microl/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products.Measurements And Main ResultsrHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products.ConclusionsOur study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

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