Hepcidin
From Standard of Care
25 amino acid antimicrobial peptide that is a controlling agent of iron absorption and iron release from macrophages.
Central regulator of iron homeostasis.
Its expression is modulated in response to body levels of iron and erythroid iron demand, hypoxia and the presence or absence of inflammation.
A small peptide reduced by the liver, controls the activity of ferroportin by attaching to it and targeting proteins for destruction in the lysozyme.
Hepcidin levels fluctuate in response to the body's need for iron causing less iron absorption with elevated levels, and lower levels of hepcidin associated with more iron absorption.
When plasma levels of iron are high its synthesis is unregulated.
Inhibits iron absorption by inducing internalization of ferroprotin, the iron transporter.
When plasma levels of iron are low the synthesis of hepcidin is down regulated leading to increased ferroportin expression on cell surface and increased dietary iron absorption and iron efflux from the macrophages.
Inhibits cellular iron export.
Synthesized primarily in the liver and is induced by elevated hepatic iron and inflammation.
Balance maintained by forces that induce and inhibit hepcidin activity.
Directly correlates between hepatic iron content and its expression.
An acute phase reactant responding to IL-1a and IL-6.
IL-6 stimulates production of hepcidin in the liver, which blocks duodenal iron absorption and down regulates expression of ferroprotein, which prevention of the release of iron from total body stores.
Increased iron stores and inflammation stimuli induce its synthesis, which reduces plasma iron levels, protects tissues from pro-oxidant conditions and restricts availability of iron to pathogens.
Modulates iron homeostasis by inducing internalization and degradation of ferroportin, the cellular iron exporter, expressed by macrophages, hepatocytes and duodenal cells.
Levels reduced below baseline during active erythropoiesis
Hypoxia and anemia are two of the major factors that trigger intestinal iron absorption, and they are independent of iron stores.
Iron refractory iron deficiency anemia (IRIDA) is a genetic process with inappropriately high production of hepcidin, limiting iron absorption and utilization.
Anemia of chronic disease is largely explained by elevated hepcidin production in response to inflammatory cytokines.
Hemochromotosis results from mutations that normally induce hepcidin, and its severity is inversely correlated with hepcidin levels.
Thalassemia and other anemias complicated by secondary iron overload, decreased iron production leads to increased iron absorption, exacerbating the iron burden of chronic transfusion treatment.
