title: Iron metabolism in the anemia of chronic disease.
abstract: BACKGROUND
  The most frequent clinical condition exemplifying the interplay between iron and immune function is the anemia of chronic disease (ACD).
  
  
  METHODS
  Based on a review of the current literature this article provides an overview of our current knowledge of iron homeostasis during inflammation, how this contributes to ACD, but also emphasizes pitfalls in diagnosing iron availability and correcting iron deficiency in this setting.
  
  
  RESULTS
  A diversion of iron from the circulation into the reticuloendothelial system and the resutling iron limitation for erythropoiesis are central for the development of ACD. Acute-phase proteins, such as hepcidin, as well as pro- and anti-inflammatory cytokines affect iron acquisition and release pathways of monocytes and macrophages thereby leading to iron restriction within the RES and systemic hypoferremia. These metabolic effects are in part exerted via cytokine-mediated modulation of transcriptional/translational expression of iron metabolism genes or by inducing labile radical formation, which then regulate the posttranscriptional regulation of cellular iron homeostasis. In addition, inflammatory processes affect macrophage iron acquisition via erythrophagocytosis while hepcidin inhibits macrophage iron release via direct interaction with the central iron export protein ferroportin.
  
  
  CONCLUSIONS
  Being aware of the effects of iron on cell mediated immune effector function and the central importance of the metal as a nutrient of invading pathogens, iron restriction within the RES harbors potential benefits for the host and may serve as a defense strategy of the body. Therapeutic manipulation of iron balance and transport under inflammatory conditions is thus a major challenge harboring both, putative beneficial and detrimental effects.
authors.affiliation: Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Medical University, Anichstr. 35, A-6020 Innsbruck, Austria. guenter@i-med.ac.at
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000740:Anemia / Q000178:diet therapy / Q000378:metabolism*; D002908:Chronic Disease; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D011990:Receptors, Transferrin / Q000502:physiology
chemical_list: D011990:Receptors, Transferrin; D007371:Interferon-gamma; D007501:Iron