Hepcidin regulation in the anemia of inflammation

Abstract

Purpose of review Anemia is prevalent in patients with infections and other inflammatory conditions. Induction of the iron regulatory hormone hepcidin has been implicated in the pathogenesis of anemia of inflammation (AI). This review outlines recent discoveries in understanding how hepcidin and its receptor ferroportin are regulated, how they contribute to AI, and how this knowledge may help guide new diagnostic and therapeutic strategies for this disease. Recent findings IL6 is a primary driver for hepcidin induction in many models of AI, but the SMAD1/5/8 pathway also contributes, likely via Activin B and SMAD-STAT3 interactions at the hepcidin promoter. Hepcidin has an important functional role in many, but not all, forms of AI, although hepcidin-independent mechanisms also contribute. In certain populations, hepcidin assays may help target therapy with iron or erythropoiesis stimulating agents to patients who may benefit most. New therapies targeting the hepcidin-ferroportin axis have shown efficacy in pre-clinical and early clinical studies. Summary Recent studies confirm an important role for the hepcidin-ferroportin axis in the development of AI, but also highlight the diverse and complex pathogenesis of this disorder depending on the underlying disease. Hepcidin-based diagnostic and therapeutic strategies offer promise to improve anemia treatment, but more work is needed in this area.

Neomorphic effects of the neonatal anemia (Nan-Eklf) mutation contribute to deficits throughout development

“…However, we do not detect any IL6, the key inducer of hepcidin and mediator of inflammation (Hom et al, 2015;Wang and Babitt, 2016).…”

Phosphate Binder, Ferric Citrate, Attenuates Anemia, Renal Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in 5/6 Nephrectomized CKD Rats

“…Intestinal absorption of iron which is mediated by divalent metal transporter and ferroportin in duodenum and proximal jejunum is tightly regulated and is inhibited by hepcidin (Zhao et al, 2013). Due to systemic inflammation, hepcidin level is significantly elevated in patients and animals with advanced CKD (Wang and Babitt, 2016). Due to impaired iron absorption, most ESRD patients are routinely treated with intravenous iron products.…”

Overview of iron metabolism in health and disease

“…The liver is the major source of circulating hepcidin that regulates systemic iron balance . Hepatocyte hepcidin expression is regulated by a number of different signals that communicate the body's need for more or less iron (Figure ) . Major hepcidin regulators include iron, erythropoietic drive, and inflammation.…”