[Iron, infection and anemia--a classical triad].

Iron plays an essential role in immunosurveillance, because of its growth promoting and differentiation inducing properties for immune cells and its interference with cell mediated immune effector pathways and cytokine activities. At the same time, iron is crucial for the proliferation of tumour cells and micro-organisms, due to its role in mitochondrial respiration and DNA synthesis. Thus, gaining control over iron homeostasis is of vital importance for the course of an infection or a tumour disease, since increased iron availability or iron overload of the immune system are associated with an unfavourable course of many of these diseases. The most frequent clinical condition demonstrating this interaction of iron and immunity is anaemia of chronic disease (ACD). ACD develops in patients with chronic activation of cellular immunity such as subjects suffering from malignancies, auto-immune disorders or infections. ACD may be seen as an immune driven disease since cytokines and their products cause (i) a diversion of iron traffic into the reticuloendothelial systems, thus limiting the availability of the metal to erythroid progenitor cells for haem biosynthesis, (ii) an inhibition of erythroid progenitor cell proliferation and (iii) blunted production and activity of erythropoietin (EPO). However, ACD may also hold some benefit by reducing iron availability to invading pathogens, thus limiting their growth, and by stimulating cell mediated immune function. The latter can be referred to the correction of an inhibitory effect of iron towards IFN-gamma induced immune effector pathways in macrophages. Whereas ACD can be easily diagnosed based on the characteristic changes of iron homeostasis, therapy of ACD is much more controversial. Where a cure of the underlying disease is impossible, transfusions for rapid correction of haemoglobin levels and human recombinant EPO can be used with varying success. The sole application of iron should be strictly avoided due to promotion of pathogen growth and impairment of immune function.