Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein.
Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor alpha (TNF-alpha), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.
Nemeth
Elizabeta
E
Department of Medicine, David Geffen School of Medicine, and the West Los Angeles Veterans Administration Hospital, University of California, Los Angeles 90095, USA.
Valore
Erika V
EV
Territo
Mary
M
Schiller
Gary
G
Lichtenstein
Alan
A
Ganz
Tomas
T
D000209:Acute-Phase Proteins / Q000145:classification / Q000652:urine*; D000740:Anemia / Q000652:urine*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology / Q000652:urine*; D016022:Case-Control Studies; D005293:Ferritins / Q000097:blood; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007239:Infections / Q000652:urine; D007249:Inflammation / Q000652:urine*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D019190:Iron Overload / Q000652:urine; D012333:RNA, Messenger / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005293:Ferritins; D007501:Iron