title: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein.
abstract: 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.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, and the West Los Angeles Veterans Administration Hospital, University of California, Los Angeles 90095, USA.
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Erika V
authors.initials: EV
authors.lastname: Valore
authors.forename: Mary
authors.initials: M
authors.lastname: Territo
authors.forename: Gary
authors.initials: G
authors.lastname: Schiller
authors.forename: Alan
authors.initials: A
authors.lastname: Lichtenstein
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
mesh_terms: 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
chemical_list: 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