Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus

Blood. 2014 Feb 20;123(8):1137-45. doi: 10.1182/blood-2013-08-521625. Epub 2013 Dec 19.


Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing hepcidin overexpression as a therapeutic strategy against AI. However, additional hepcidin-independent mechanisms contribute to AI, which are likely mediated by a direct effect of inflammatory cytokines on erythropoiesis. In this study, we used wild-type, hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were investigated. BA-treated wild-type mice showed increased expression of hepcidin and inflammatory cytokines, as well as transitory suppression of erythropoiesis and shortened red blood cell lifespan, all of which contributed to the severe anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed milder anemia and faster recovery compared with normal mice. Moreover, they exhibited different patterns in the development and resolution of anemia, supporting the notion that interleukin 6 and hepcidin play distinct roles in modulating erythropoiesis in AI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / genetics
  • Anemia / immunology*
  • Anemia / microbiology
  • Animals
  • Bone Marrow / immunology
  • Brucella abortus*
  • Brucellosis / complications
  • Brucellosis / immunology*
  • Disease Models, Animal
  • Erythropoiesis / immunology
  • Female
  • Hepcidins / genetics
  • Hepcidins / immunology*
  • Hot Temperature
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Recovery of Function / immunology


  • Hamp protein, mouse
  • Hepcidins
  • Interleukin-6
  • interleukin-6, mouse