Figure 1.

Decrease in iron recycling in the presence of inflammation: iron metabolism in critically ill patients. Most of the iron available for erythropoiesis comes from the catabolism of senescent red blood cells (RBC) by the macrophages in the reticuloendothelial system. Under normal conditions, there is a balance between the iron transport paths and the iron stores: serum iron, 9–27 μmol/l; transferrin, 3–6 g/l; transferrin saturation (sat.), 30–50%; ferritin, 50–150 μg/l. In the presence of inflammation, the synthesis of ferritin is increased by IL-1 and by tumor necrosis factor (TNF). Hypoferremia rapidly sets in due to an increase in the iron-binding capacity of ferritin to the detriment of transferrin. IL-l also stimulates lactoferrin synthesis. Iron bound to lactoferrin is captured by the macrophages and is stored in the form of ferritin. Hepcidin could be a central mediator of iron sequestration in macrophages. Grey arrows, pathways increased by inflammation; broken arrows, pathways decreased by inflammation.