Modification of iron regulation by the inflammatory response.
Iron is an essential compound for 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. Thus, the reticuloendothelial system has generated sophisticated strategies to control iron metabolism in general and the handling of the metal within immune cells. Cytokines, immune-cell-derived radicals, and acute-phase proteins affect the regulation of iron homeostasis at different levels ranging from transcriptional interference with iron genes to modulation of iron transport capacities of transmembrane iron channels. Thus, under inflammatory conditions a diversion of iron traffic from the circulation to storage sites of the reticuloendothelial system occurs. This results in an iron-restricted erythropoiesis and the development of anemia, termed 'anemia of chronic disease'. The development of hypoferremia and hyperferritinemia under chronic inflammatory conditions may also harbor some positive effects: first, by limiting the availability of the essential nutrient and growth factor iron to invading microbes and tumor cells, thus blocking their proliferation, and secondly by strengthening cell-mediated immune effector pathways directed against invading pathogens. Studying iron metabolism under inflammatory conditions will extend our knowledge and improve our understanding of regulatory pathways in host-pathogen interactions during infection and cancer, and may hold the key for future therapeutic developments for the treatment of such diseases as well as for anemia of chronic disease.
Weiss
Günter
G
Department of General Internal Medicine, Clinical Immunology and Infectious Diseases Medical University, Anichstr. 35, A-6020 Innsbruck, Austria. guenter.weiss@uibk.ac.at
D000209:Acute-Phase Proteins / Q000378:metabolism; D000740:Anemia / Q000209:etiology / Q000276:immunology; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*
D000209:Acute-Phase Proteins; D016207:Cytokines; D007501:Iron