These studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL- 6-hepcid in axis is responsible for the hypoferremia of inflammation.
It is reported that hepcidin bound to ferroportin in tissue culture cells, leading to decreased export of cellular iron and the posttranslational regulation of ferroports by hePCidin may complete a homeostatic loop.
A new hormone, erythroferrone (ERFE), is identified that mediates hepcidin suppression during stress erythropoiesis, and is greatly increased in Hbbth3/+ mice with thalassemia intermedia, where it contributes to the suppression of hePCidin and the systemic iron overload characteristic of this disease.
The positional cloning of the locus associated with juvenile hemochromatosis is reported and the identification of a new gene crucial to iron metabolism is identified, now called HFE2, whose protein product the authors call hemojuvelin.
The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
The first serum enzyme-linked immunosorbent assay for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure, yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the etiology of iron disorders.
The hepcidin-ferroportin axis is the principal regulator of extracellular iron homeostasis in health and disease, and is a promising target for the diagnosis and treatment of iron disorders and anemias.
Recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection are reviewed, emphasizing aspects that are applicable to human health and disease.