Anemia of inflammation: The hepcidin link

Purpose of review: The anemia of inflammation has been associated for nearly two decades with elevated cytokine levels, but the primary mediator of this condition was unknown. Recently hepcidin antimicrobial peptide has emerged as the hormone that links the type II acute phase response to iron handling and erythropoiesis. Recent findings: Hepcidin antimicrobial peptide likely modulates iron transport from macrophages and enterocytes to red blood cell precursors as a consequence of its interaction with SLC40A1/ferroportin, the only known transporter that facilitates iron egress. Insights into the regulation of hepcidin antimicrobial peptide expression by known iron metabolic proteins such as HFE, hemojuvelin, and transferrin receptor 2 are expanding the understanding of the genetic circuitry that controls iron absorption and utilization. Summary: Increasingly, experiments suggest the hepatocyte is not just the iron storage depot but is the 'command central' for the maintenance of iron homeostasis. It receives multiple signals related to iron balance and responds via transcriptional control of hepcidin antimicrobial peptide.