Theurl I, Aigner E, Theurl M, Nairz M, Seifert M, Schroll A, Sonnweber T, Eberwein L, Witcher DR, Murphy AT, Wroblewski VJ, Wurz E, Datz C, Weiss G.
The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux upon binding to the iron export protein ferroportin. Many patients, however, present with both, ACD and iron deficiency anemia (ACD/IDA), the later due to chronic blood loss. We used a rat model of ACD due to chronic arthritis and mimicked ACD/IDA by additional phlebotomy in order to define differing iron regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans suffering from ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals suffering from ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA individuals, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/ IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients