What is hepcidin telling us about the natural history of cystic fibrosis?

Abstract

An expanding body of evidence suggests that iron homeostasis is abnormal in cystic fibrosis (CF). Concentrations of iron in the sputum and bronchoalveolar lavage (BAL) fluid of healthy unaffected persons are <16 μmol/l [1,2] and 0.13 μmol/l [3], respectively, whereas that of CF sputum generally exceeds 30 μmol/l and can be as high as 200 μmol/l [1,2]. Using an in-vitro co-culture model of polarized human bronchial epithelial cells and Pseudomonas aeruginosa (Pa), Moreau-Marquis et al. [4] first observed that F508del-CFTR increased the iron content of airway surface liquid, a phenomenon that promoted Pa biofilm growth. Thus, the genetic defect found in most CF patients [5] plausibly contributes to the persistence of this and other pathogens by increasing the availability of a typically scarce micronutrient. Among CF adults, those who have more iron in their sputum not only have higher circulating interleukin-6 (IL-6) levels but also have lower blood iron stores, or relative hypoferremia [6]. IL-6 drives hepatic production of the small peptide hormone, hepcidin-25, which potently induces hypoferremia [7].