The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hepcidin expression, have led many to consider it the major mediator of ACD. However, if hepcidin is the major factor responsible for ACD, then it should also contribute to the impaired erythropoiesis observed in this syndrome. Erythroid colony formation in vitro was inhibited by hepcidin at erythropoietin (Epo) concentrations less than or equal to 0.5 U/mL but not at Epo 1.0 U/mL. At Epo concentrations of 0.3 U/mL, HCD57 erythroleukemia cells exposed to hepcidin exhibit decreased expression of the antiapoptotic protein pBad compared with controls. These studies suggest that hepcidin may contribute to anemia in ACD not only through effects on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival.

The hepatic antimicrobial protein, hepcidin, is implicated in duodenal iron absorption and mobilization. Overexpression of the hepcidin gene is associated with a hypoferraemic, microcytic, iron-refractory anaemia. On the basis of these observations, it has been proposed that hepcidin is a mediator of the common clinical syndrome, anaemia of chronic disease (ACD), and recent findings evaluating urinary hepcidin production in patients support this hypothesis. In the present report, serum hepcidin concentrations were measured in 55 specimens submitted for ferritin determination, and in 37 specimens collected from anaemic patients undergoing diagnostic bone marrow examination. The serum hepcidin concentration exhibited a statistically significant correlation with serum ferritin concentrations in both patient subsets. No statistically significant correlations were observed between serum hepcidin and other laboratory markers of iron status or anaemia diagnosis. Serum hepcidin does not appear to correlate as well with clinical diagnosis as urinary hepcidin, suggesting that a better understanding of the clearance and metabolism of this protein is required to understand fully its potential contribution to the pathogenesis of ACD.

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