Figure 4. Hypothetic model of the iron metabolism in severely anemic children.

Severe anemia is associated with severe infections [7]; the associated high levels of IL-6 induce hepcidin [12]. Although in severe anemia hypoxia stimulates the kidneys to produce erythropoietin; the erythropoietin induced erythropoietic drive will down-regulate hepatic hepcidin expression, and may overrule hepcidin stimulation of IL-6. The resulting low hepcidin values are associated with decreased degradation of the cellular iron exporter ferroportin; in iron replete subjects or during iron supplementation/treatment this will lead to a rise in plasma iron levels [12]. In infection endemic areas this may increase infection risk [5], [40]. In addition inflammatory related factors possibly inhibit erythroblast iron incorporation. CRP: c-reactive protein; ery: erythroblast; epo: erythropoietin; Fe: plasma iron; FPN: ferroportin; hep: hepcidin-25; IL-6; interleukin 6.