Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications.
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 on binding to the iron export protein ferroportin. Many patients, however, present with both ACD and iron deficiency anemia (ACD/IDA), the latter resulting from chronic blood loss. We used a rat model of ACD resulting from chronic arthritis and mimicked ACD/IDA by additional phlebotomy 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 with ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals with ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA persons, 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.
Theurl
Igor
I
Department of Internal Medicine I, Medical University of Innsbruck, Austria.
Aigner
Elmar
E
Theurl
Milan
M
Nairz
Manfred
M
Seifert
Markus
M
Schroll
Andrea
A
Sonnweber
Thomas
T
Eberwein
Lukas
L
Witcher
Derrick R
DR
Murphy
Anthony T
AT
Wroblewski
Victor J
VJ
Wurz
Eva
E
Datz
Christian
C
Weiss
Guenter
G
D000740:Anemia / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000032:analysis; D002908:Chronic Disease; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D000098742:Ferroportin; D007501:Iron