Erythropoietin promotes functional recovery in a mouse model of postoperative ileus

Background: Dysmotility and postoperative ileus (POI) are major clinical problems after surgical trauma and it is associated with increased intestinal inflammation and oxidative stress. Despite the high occurrence of POI following intra-abdominal surgeries, no effective treatment is currently available. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine with potent anti-inflammatory and anti-oxidative properties, and it is an FDA approved medicine for clinical use. While both EPO and EPO receptors (EPOR) are widely expressed in the gut, the role of EPO in POI is largely unknown. This study was designed to explore the possible beneficial effect of EPO in a mouse model of POI. Methods: Mice were subjected to intestinal manipulation to induce standard POI and intestinal transit time was determined at 24-h post-injury with or without EPO treatment (5000 units/kg, once, IP, immediately after intestinal trauma). Intestinal samples were harvested for histological and immunohistochemical analysis. Results: Systemic EPO significantly improved intestinal transit time compared with control group and it was associated with significantly increased levels of tissue macrophages and reduced levels of oxidative stress. Conclusions and Inferences: This is the first pre-clinical study to document novel beneficial effects of EPO in gut dysmotility and our findings suggest that the beneficial effects of EPO in POI is predominantly mediated by its anti-oxidative and immunomodulatory properties.