IRON DEPRIVATION INCREASES ERYTHROPOIETIN PRODUCTION IN-VITRO, IN NORMAL SUBJECTS AND PATIENTS WITH MALIGNANCY

Although tissue hypoxia is the major stimulus for erythropoietin (EPO) production, serum EPO (sEPO) levels at any given Hb in iron-deficienc y anaemia are relatively higher than in other anaemias. Iron chelators stimulate erythropoiesis in anaemia of chronic disease via unknown me chanisms. A recent study suggested that deferoxamine (DFO) regulates s teady-state EPO RNA. Here we report that altered intracellular iron ba lance regulates EPO production both in vitro and in two unique clinica l trials. In vitro, both iron chelation with DFO and blockade of Tf-me diated iron uptake with anti-Tf receptor antibody 42/6, stimulated EPO production in serum-deprived hepatoma cells. Conversely, iron repleti on by haemin, inhibited EPO production in these cells. In clinical stu dies, sEPO levels rose in adult volunteers treated with UFO coupled to hydroxyethyl starch (HES-DFO) and in patients with advanced malignanc y treated with anti-Tf receptor antibody 42/6, in a time- and dose-dep endent manner. These studies indicate intracellular iron balance regul ates EPO production in humans.