Hepcidin is the master regulator of iron homeostasis. Hepcidin regulates extracellular iron in response to changes in dietary and systemic iron, anemia, hypoxia, inflammation and erythropoiesis. Hepcidin is also an acute phase protein that is increased in anemia of inflammation, regulated by the inflammatory cytokine IL-6. Hepcidin inhibits cellular iron efflux by binding to and inducing internalization of the sole known iron exporter ferroportin, which mediates iron absorption from intestine and iron recycling by macrophages.
Synthetic hepcidin injected into mice rapidly lowers serum iron levels, confirming its central role in regulating iron homeostasis. Hepcidin is the master regulator of intestinal iron absorption, recycling of senescent RBCs and iron via macrophages, and efflux to plasma from hepatocytes in humans.