Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

Abstract

Current pharmacotherapy for acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is not optimal, while the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a number of preclinical studies have revealed beneficial effects of EPO administration in various experimental models of ALI. Taken together, this treatment strategy is not a single mediator approach, but it rather provides protection by modulating multiple levels of early signaling pathways involved in apoptosis, inflammation and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO appears to confer vascular protection by promoting angiogenesis. However, only preliminary studies exist and more experimental and clinical studies are necessary for the clarification of the efficacy and potentially cytoprotective mechanisms of EPO action. In addition to the attempts to optimize the dose and timing of EPO administration, it would be of great value to minimize any potential toxicity, which is essential for EPO to fulfil its role as a potential candidate for the treatment of ALI in routine clinical practice. The present article reviews recent advances that have elucidated biological and biochemical activities of EPO which may be potentially applicable for ALI/ARDS management.

Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats

“…Accumulating evidence has indicated that erythropoietin exerts anti-apoptotic and tissue-protective effects in a variety of human diseases, such as myocardial infraction (16–18), diabetes mellitus (19), spinal cord injury (20–22), ischemia-reperfusion (I/R)-induced kidney injury (23) and acute lung injury (24,25). Galeano et al reported that recombinant human EPO (rhuEPO) may be an effective therapeutic approach for improving clinical outcomes by enhancing the wound content of vascular endothelial growth factor (VEGF) following thermal injury (26).…”

Erythropoietin Promotes the Protective Properties of Transplanted Endothelial Progenitor Cells Against Acute Lung Injury via PI3K/Akt Pathway

“…Erythropoietin has long been reported for its pleiotropic effects against ALI/ARDS (11). Together with other researches, our previous articles focused on the protective effects of EPO on ALI, which also presented a significant improvement on lung tissue recovery.…”

“…Recent studies revealed that erythropoietin (EPO) played as a multifunctional endogenous mediator participating in various pathophysiological processes during critical illness (11). It is also reported as a stimulant for EPC proliferation and mobilization and may exert its protective effects on endothelial cells to maintain the integrity of pulmonary endothelium during ALI/ARDS (11Y13).…”

Gene therapy for radioprotection

“…Studies have examined Epo as a protective agent in ischemia-reperfusion injuries of the heart and kidney 89 and in acute lung injury models. 90 …”