Albertine Donker

Chapter 7 248 DISCUSSION Our data provide age- and sex-specific values for hepcidin-25 and its ratios to parameters reflecting circulating and stored iron for healthy Dutch children, as assessed by a standardized assay. These values can be used as for any other hepcidin assay worldwide that is standardized using the same 2 nd RM for calibration. 22 We found no difference between serum hepcidin levels between males and females. Serum ferritin as a reflection of iron stores was the most important correlate of serum hepcidin, however the variance in serum hepcidin levels that could be explained by serum ferritin levels was considerably lower (R 2 15.1 for males, 7.9% for females) than for adults (R 2 56 for men, 60% for women). 20 Although mice studies suggest that circulating iron also influences serum hepcidin concentration, 42,43 TSAT was only marginally associated with serum hepcidin levels, as seen in adults. 20 We obtained the serum hepcidin/ferritin ratio and the TSAT/hepcidin ratio to get insights in the set off of the hepcidin regulatory pathway relative to stored iron (ferritin) and circulating iron (TSAT) with aging, respectively, as reported before. 6 Interestingly, serum hepcidin relative to ferritin and TSAT was lower for older compared to younger children and also compared to adults. 21 This was reflected in a lower hepcidin/ferritin ratio and an increased TSAT/ hepcidin ratio, which implies that the extent of induction of the different regulatory pathways of hepcidin by both iron stores and circulating iron in healthy children and adolescents are dependent on age. 42,43 These age-specific differences in hepcidin set points might be an expression of the two opposite operating forces considering iron metabolism. Iron is indispensable for the production of heme proteins and for other vital functions requiring a persistent flow of iron into the blood stream, especially during periods of rapid growth during infancy. A recent study of Armitage et al indeed observed that antecedent weight gain was negatively associated with serum hepcidin levels in Gambian infants. 39 However, the virulence of infectious organisms depends on their ability to assimilate iron from their host. Therefore, humans and other mammals have to cope with piracy of iron by pathogens in order to battle against infections. 44 Since hepcidin has the