title: Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus.
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.
authors.affiliation: Department of Pediatric Hematology-Oncology, Children's and Cancer Blood Foundation Laboratories, Weill Cornell Medical College, New York, NY;
authors.forename: Sara
authors.initials: S
authors.lastname: Gardenghi
authors.forename: Tom M
authors.initials: TM
authors.lastname: Renaud
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meloni
authors.forename: Carla
authors.initials: C
authors.lastname: Casu
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Crielaard
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bystrom
authors.forename: Noa
authors.initials: N
authors.lastname: Greenberg-Kushnir
authors.forename: Barbra J
authors.initials: BJ
authors.lastname: Sasu
authors.forename: Keegan S
authors.initials: KS
authors.lastname: Cooke
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
mesh_terms: D000740:Anemia / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002003:Brucella abortus; D002006:Brucellosis / Q000150:complications / Q000276:immunology*; D004195:Disease Models, Animal; D004920:Erythropoiesis / Q000276:immunology; D005260:Female; D064451:Hepcidins / Q000235:genetics / Q000276:immunology*; D006358:Hot Temperature; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020127:Recovery of Function / Q000276:immunology
chemical_list: C579599:Hamp protein, mouse; D064451:Hepcidins; D015850:Interleukin-6; C577686:interleukin-6, mouse