Hepcidin synthesis in the liver and its effects on iron metabolism. Hepatic sinusoids (S, pink) are lined by endothelial cells (green) and Kupffer cells (K, green). Exposure of these cells to microbes or highly iron-saturated transferrin (Fe/Tf) causes the release of IL-6 and possibly other signals (red arrows) that act on hepatocytes (H, light blue cells) to induce the synthesis and secretion of hepcidin (yellow arrows). Plasma hepcidin (large yellow arrows) inhibits iron uptake in the duodenum and iron release from macrophages in the spleen and elsewhere.