• interleukin-6
• hepcidin
• iron absorption
• hereditary haemochromatosis
• anaemia of chronic disease

In health, the body content of iron is maintained within fairly narrow limits to provide sufficient iron for synthesis of ferroproteins essential for oxygen transport and catalysis yet avoid the toxic effects of excess. Early experiments provided tantalising evidence for a humoral regulatory factor. Serum obtained from iron repleted rats inhibited iron absorption in normal rat duodenum.¹ For many years this putative factor remained elusive. However, recent studies indicate that a peptide hormone, hepcidin, may play a crucial regulatory role in normal iron homeostasis, haemochromatosis, and the anaemia of chronic disease.²

Hepcidin was identified not from studies of iron homeostasis but from investigation of novel antimicrobial peptides in body fluids. Krause and colleagues³ screened human blood ultrafiltrate (a source of the antimicrobial peptides defensins) for small cysteine rich peptides. A 25 amino acid peptide with a mass of 2.7 kDa was found, containing a remarkable eight disulphide bonded cysteine residues. It showed antimicrobial activity against some bacteria and the yeast Saccharomyces cerevisiae. Quantitative reverse transcription-polymerase chain reaction showed predominant expression in liver. The peptide was called LEAP-1 (liver-expressed antimicrobial peptide).³ The cDNA sequence predicted an 84 amino acid pre-propeptide with two cleavage sites. The first predicts cleavage of the N terminal endoplasmic reticulum targeting signal sequence (amino acids 1–24). The second consensus cleavage site for prohormone convertases would yield the central prodomain (amino acids 25−59) plus the 25 amino acid C terminal peptide (also called hepcidin-25; amino acids 60–84). A slightly truncated 20 amino acid peptide was also found (hepcidin 20; amino acids 65–84). Independently, Park and colleagues⁴ isolated the same cysteine rich peptide from human urine and named it …