title: A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin.
abstract: Anemia is a common complication of infections and inflammatory diseases, but the few mouse models of this condition are not well characterized. We analyzed in detail the pathogenesis of anemia induced by an injection of heat-killed Brucella abortus and examined the contribution of hepcidin by comparing wild-type (WT) to iron-depleted hepcidin-1 knockout (Hamp-KO) mice. B abortus-treated WT mice developed severe anemia with a hemoglobin nadir at 14 days and partial recovery by 28 days. After an early increase in inflammatory markers and hepcidin, WT mice manifested hypoferremia, despite iron accumulation in the liver. Erythropoiesis was suppressed between days 1 and 7, and erythrocyte destruction was increased as evidenced by schistocytes on blood smears and shortened red blood cell lifespan. Erythropoietic recovery began after 14 days but was iron restricted. In B abortus-treated Hamp-KO compared with WT mice, anemia was milder, not iron restricted, and had a faster recovery. Similarly to severe human anemia of inflammation, the B abortus model shows multifactorial pathogenesis of inflammatory anemia including iron restriction from increased hepcidin, transient suppression of erythropoiesis, and shortened erythrocyte lifespan. Ablation of hepcidin relieves iron restriction and improves the anemia.
authors.affiliation: Department of Medicine, and.
authors.forename: Airie
authors.initials: A
authors.lastname: Kim
authors.forename: Eileen
authors.initials: E
authors.lastname: Fung
authors.forename: Sona G
authors.initials: SG
authors.lastname: Parikh
authors.forename: Erika V
authors.initials: EV
authors.lastname: Valore
authors.forename: Victoria
authors.initials: V
authors.lastname: Gabayan
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
mesh_terms: D000208:Acute Disease; D000740:Anemia / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002003:Brucella abortus; D002006:Brucellosis / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004920:Erythropoiesis / Q000276:immunology; D006461:Hemolysis / Q000276:immunology; D064451:Hepcidins / Q000235:genetics / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D007501:Iron / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C579599:Hamp protein, mouse; D064451:Hepcidins; D007501:Iron