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Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus.
- Source :
-
Blood [Blood] 2014 Feb 20; Vol. 123 (8), pp. 1137-45. Date of Electronic Publication: 2013 Dec 19. - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Anemia genetics
Anemia microbiology
Animals
Bone Marrow immunology
Brucellosis complications
Disease Models, Animal
Erythropoiesis immunology
Female
Hepcidins genetics
Hot Temperature
Interleukin-6 genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Recovery of Function immunology
Anemia immunology
Brucella abortus
Brucellosis immunology
Hepcidins immunology
Interleukin-6 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24357729
- Full Text :
- https://doi.org/10.1182/blood-2013-08-521625