Figure 1. Hepcidin-mediated regulation of iron homeostasis.

(A) Increased hepcidin expression by the liver results from inflammatory stimuli. High levels of hepcidin in the bloodstream result in the internalization and degradation of the iron exporter ferroportin. Loss of cell surface ferroportin results in macrophage iron loading, low plasma iron levels, and decreased erythropoiesis due to decreased transferrin-bound iron. The decreased erythropoiesis gives rise to the anemia of chronic disease. (B) Normal hepcidin levels, in response to iron demand, regulate the level of iron import into plasma, normal transferrin saturation, and normal levels of erythropoiesis. (C) Hemochromatosis, or iron overload, results from insufficient hepcidin levels, causing increased iron import into plasma, high transferrin saturation, and excess iron deposition in the liver.