Erythropoietin as an Immunomodulating Agent

Erythropoietin (EPO) is a glycoprotein produced by peritubular capillary epithelial kidney cells in response to hypoxia to control erythropoiesis. It stimulates growth and differentiation of red blood cells progenitors and protects them from apoptosis by binding to receptor (EPO-R) on CFU-E (erythroid colony-forming unit) and BFU-E (erythroid burst-forming unit) colonies. Although it seems that primary role of EPO is the regulation of red cells production, EPO-R has been found in/on other tissues and cells, including human polymorphonuclear leukocytes, monocytes and lymphocytes. Both EPO-R structure and its presence on these cells suggest that beyond erythropoietic function, EPO might possess some immunomodulatory properties. Progress of chronic kidney disease (CKD) gradually leads to kidney failure, uremia, hypertension and anemia resulting from decreased EPO production and presence of uremic toxins and proiflammatory cytokines. At the same time, CKD patients also show signs of the deficiency state in both cell mediated and humoral immunity, which is even deepened by dialysis procedure. High levels of proinflammatory cytokines produced by chronically activated monocytes and decreased IL-2 level reflecting weakened T lymphocytes function are observed. Deficient T lymphocytes responses lead to impaired humoral immunity presented by the decreased immunoglobulin levels in response to hepatitis B vaccination and increased frequency of different infections. Since late 80s recombinant human erythropoietin (rhEPO) is commonly used for treatment of anemia related to chronic kidney disease (CKD). Current review describes immunological aspects of rhEPO therapy in CKD patients. The aim of this work is to pay attention to the fact that observed improvement of the immunological responses described in last 15 years in CKD patients is not only the result of anemia correction during rhEPO treatment. Changes of crucial activation and co-stimulation antigens of T lymphocytes of rhEPO treated CKD patients along with EPO-R presence on human leukocytes indicate that EPO/rhEPO can directly influence immunological responses.