Organ-protective and immunomodulatory effects of erythropoietin--an update on recent clinical trials

Erythropoietin (EPO) belongs to a group of pharmacological agents with multifunctional effects. EPO was originally acknowledged as the main regulator of erythropoiesis, but it also exhibits several extra haematopoietic properties, such as promoting the maintenance of homeostasis of cells under stress. These pleiotropic effects have been extensively investigated in preclinical models including models of ischaemic-reperfusions injuries, inflammation, neuroprotection, neovascularisation and wound healing. Promising effects of EPO have especially been reported in models of ischaemic-reperfusions injuries. The mechanisms by which EPO exerts these organ-protective effects are not completely understood, although anti-apoptotic, anti-inflammatory and anti-oxidative properties have been described. Activation of the EPO receptor initiates several intracellular signalling systems, such as, phosphatidylinositol 3-kinase, STAT5, mitogen-activated protein kinase and nuclear factor-kappa B. These pathways are recognized as involved in the cellular response to stress and regulation of apoptosis. Although EPO has been demonstrated to be effective in animal models, the effect has not been clearly demonstrated in clinical trials. This MiniReview gives a brief introduction to the pleiotropic effects of EPO, the evidence of organ protection in animal models, and discusses the disappointing results obtained from recent clinical trials.