The role of hepcidin in systemic iron homeostasis. (a) In healthy individuals, hepcidin production increases in response to increasing levels of transferrin-bound serum iron and iron stores. Hepcidin internalizes and degrades the iron transporter ferroportin, restricting the export of iron from enterocytes and from iron stores in hepatocytes and macrophages, to restore normal iron levels. (b) In inflammatory conditions, hepcidin production increases in response to inflammatory cytokines such as IL-6, disrupting the usual homeostatic mechanisms. Ferroportin is internalized and degraded, reducing transmembrane export of iron, and the availability of iron to bind to transferrin is restricted.