title: Iron and the risk of infection.
abstract: BACKGROUND
  During bacterial infection, pathogen and host compete for iron (Fe). The inflammatory response associated with infection shifts Fe from the circulation into storage, resulting in hypoferremia and iron-deficient erythropoiesis, and ultimately contributing to the anemia of inflammation.
  
  
  METHODS
  In this article, we review the mechanisms of Fe acquisition and sequestration. Bacteria employ both membrane-bound transferrin receptors and high-affinity iron-binding proteins called siderophores to acquire Fe. Humans utilize the iron-binding proteins lactoferrin, transferrin, and ferritin to move Fe away from sites of infection and into storage. Synthesis and action of these proteins are regulated by inflammatory cytokines.
  
  
  RESULTS
  Iron overload leads to inhibition of IFN-gamma, TNF-alpha, IL-12, and nitric oxide formation as well as impairment of macrophage, neutrophil, and T-cell function. Injection of Fe into mice and rats markedly increases the virulence of several pathogens. Studies in hemodialysis patients have documented an association between infection and increased ferritin concentration as a surrogate marker for Fe overload.
  
  
  CONCLUSIONS
  Humans respond to infection with inflammatory cytokine-induced hypoferremia. This association, as well as the growing literature linking Fe to both impaired immunity and heightened microbial virulence, calls into question the value of Fe supplementation during inflammation and infection.
authors.affiliation: Department of Surgery, Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: Fredric M
authors.initials: FM
authors.lastname: Pieracci
authors.forename: Philip S
authors.initials: PS
authors.lastname: Barie
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D051381:Rats
chemical_list: D007166:Immunosuppressive Agents; D007501:Iron