Albertine Donker

Chapter 2 58 levels are favorable in the context of host defense against extracellular pathogens, 27 outweighing the risk of ID. 3,4 We found the opposite in adolescents, i.e. relatively low hepcidin levels relative to body iron, possibly due to the effect of sex hormones, 7 and as part of an adaptive response in order to obtain sufficient iron to meet the high requirements for the growth spurt typical of puberty. We therefore hypothesized that the set point of systemic iron homeostasis might change during lifetime to adapt to different conditions for which a high amount of iron is relatively favorable or not. 43 This point needs further confirmation in larger studies since in our study young children and children from a non-Western European descent were underrepresented. We therefore advocate calibration of worldwide hepcidin assays using secondary (matrix) reference material that has been value assigned by primary reference material. Iron availability versus iron restriction in inflammation Since many of both stimulating and suppressing stimuli might be present simultaneously, the hepcidin level in the human body reflects the net effect of these multiple key signals, depending on the relative strength of each stimulus. 45 In adult ICU patients, serum hepcidin levels decline with the onset of ID. 46 In a recent study in women diagnosed with mild iron deficiency anemia (IDA), mild inflammation did not increase serum hepcidin levels. 47,48 Also in severely anemic children, hepcidin tends to be low even in de presence of inflammation. 46,49 However, other data suggest that even low-grade inflammation induce and increase of serum hepcidin levels, resulting in hepcidin-mediated blockade of iron absorption. 50 Whether iron acquisition will get priority over iron restriction in case of a combination of ID and inflammation, is still unclear, and might depend on the degree of these opposing forces. We hypothesize that inflammation initially induces hepcidin synthesis resulting in iron-restricted erythropoiesis, 51 until body iron decreases below a critical threshold (and anemia occurs). Below this threshold, hepcidin production will drop in order to guarantee sufficient iron supply to the erythroblasts for the productions of erythrocytes, preventing severe anemia.