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.

[1]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[2]  G. Ramadori,et al.  Cytokines and the hepatic acute phase response , 1997, The Journal of pathology.

[3]  Peter Schulz-Knappe,et al.  LEAP‐1, a novel highly disulfide‐bonded human peptide, exhibits antimicrobial activity , 2000, FEBS letters.

[4]  W. Sly,et al.  Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Bruno Turlin,et al.  A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload* , 2001, The Journal of Biological Chemistry.

[6]  Christina H. Park,et al.  Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver* , 2001, The Journal of Biological Chemistry.

[7]  C. Beaumont,et al.  Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. Beaumont,et al.  Severe iron deficiency anemia in transgenic mice expressing liver hepcidin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Burns,et al.  Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge. , 2002, European journal of biochemistry.

[10]  F. Torti,et al.  Regulation of ferritin genes and protein. , 2002, Blood.

[11]  H. Vogel,et al.  The Solution Structure of Human Hepcidin, a Peptide Hormone with Antimicrobial Activity That Is Involved in Iron Uptake and Hereditary Hemochromatosis* 210 , 2002, The Journal of Biological Chemistry.

[12]  H. Vogel,et al.  Solution Structure of Hepcidin-20 , 2002 .

[13]  M. Loda,et al.  Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. , 2002, Blood.

[14]  Gaël Nicolas,et al.  The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. , 2002, The Journal of clinical investigation.