Liver Macrophages (Kupffer cells) As Novel Targets of Erythropoietin

Erythropoietin (EPO) synthesized by the kidney and by the fetal liver is the major hormone that drives mammalian erythropoiesis. It is thus used in treatment of anemia, associated with chronic renal failure, as well as for alleviating chemotherapy or radiotherapy induced anemia in certain cancer patients. The physiological role of EPO is to regulate production of red blood cells via its receptor, EPO-R. However, EPO-R was found also in various other cell types, as shown also by us, suggesting that EPO may have pleiotropic activities. Originally, we have shown EPO effects on bone-marrow derived macrophages. We now report on EPO effects on liver macrophages. Using transgenic mice, overexpressing human EPO (tg6 mice), we found that they have a 2 fold increased level of F4/80 positive liver macrophages, compared to wt mice (p=0.01). In addition, C57bl/6 wt mice, injected 3 times a week with 180 U/ml of recombinant human EPO (rHuEPO) displayed a 2 fold increase in the percentage of F4/80 expressing cells (p=0.02), and in double positive F4/80 and CD11b expressing cells (p=0.03), compared to their untreated littermates. Similar results were observed in an experimental murine model of multiple myeloma (5T33). Hence, 5T33 MM mice that were treated with rHuEPO (10 consecutive days of 30 U/ml followed by 3 weekly injections of 30 U/ml for 2 weeks), presented a 2.5 fold increase (p=0.0004) and a 3 fold increase (p The first two authors contributed equally to this study. This work was supported by the FP7-Health European commission EpoCan grant (282551). Disclosures No relevant conflicts of interest to declare.