Potential anti-inflammatory effect of erythropoietin in non-clinical studies in vivo: A systematic review.

Erythropoietin (EPO) is a hypoxia-induced hormone produced in adult kidneys with erythropoietic and non-erythropoietic effects. In vivo studies represent an important role to comprehend the efficacy and safety in the early phase of repurposing drugs. The aim is to evaluate the potential anti-inflammatory effect of EPO observed in animal models of disease. Following PRISMA statements, electronic database Medline via PubMed platform was used to search articles with the research expression ((erythropoietin [MeSH Terms]) AND (inflammation [MeSH Terms]) AND (disease models, animal [MeSH Terms])). The inclusion criteria were original articles, studies where EPO was administered, studies where inflammation was studied and/or evaluated, non-clinical studies in vivo with rodents, and articles published in English. Thirty-six articles met the criteria for qualitative analysis. Exogenous EPO was used in models of sepsis, traumatic brain injury, and autoimmune neuritis, with an average of 3000 IU/Kg for single and multiple doses, using mice and rats. Biomarkers such as immune-related effectors, cytokines, reactive oxygen species, prostaglandins, and other biomarkers were assessed. EPO has been recognized as a multifunctional cytokine with anti-inflammatory properties, showing its significant effect both in acute and chronic models of inflammation. Further non-clinical studies are suggested for the enlightenment of anti-inflammatory mechanisms of EPO in lower doses, allowing us to understand the translational data for humans.