Iron is an essential element for microbes, plants, and animals. Hepcidin is a small peptide manufactured in the liver that regulates intestinal iron absorption, iron recycling by macrophages, and iron metabolism from hepatic stores. It also plays an important role in development of anemia of inflammation and pathogenesis of hereditary hemochromatosis. Hepcidin has a negative effect on iron metabolism. Secretion is increased in iron loading and decreased by anemia and hypoxia. During infection and inflammation, production increases markedly, resulting in anemia of inflammation because iron is sequestered in macrophages, liver cells, and erythrocytes. This is beneficial to the host because it limits iron availability to invading microbes. Mammals, including humans, cannot excrete excess iron, so iron is regulated by iron uptake as well as by a feedback mechanism. Experiments in mice have shown that hepcidin deficiencies or abnormalities lead to the development of hemochromatosis. Research on hepcidin will be important in finding ways to diagnose and treat hereditary and acquired hemochromatosis. Canine hepcidin has recently been cloned and sequenced; human hepcidin is more homologous with canine hepcidin than with other species. Dogs may be suitable animal models of disease; if so, the veterinarian's knowledge of iron-related diseases in dogs will be increased.

COMMENTARY: Seldom does a breakthrough in our knowledge of physiology unravel a clinical mystery. For decades we have observed the anemia of chronic disease without understanding the causes. The identification of hepcidin, a cysteine-rich polypeptide acute-phase reactant produced by the liver, seems to play a critical role in regulation of iron metabolism.

Hepcidin-a regulator of intestinal iron absorption and iron recycling by macrophages. Ganz T. BEST PRACT RES CLIN HAEMATOL18:171-182, 2005.

Molecular cloning and expression of canine hepcidin. Fry MM, Liggett JL, Baek J. VET CLIN PATHOL 33:223-227, 2004.