title: Late stage erythroid precursor production is impaired in mice with chronic inflammation.
abstract: BACKGROUND
  We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active.
  
  
  METHODS
  We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence.
  
  
  RESULTS
  Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice.
  
  
  CONCLUSIONS
  Our results suggest that chronic inflammation inhibits late stages of erythroid production in the turpentine-induced sterile abscess model and induces features of impaired erythropoiesis which are distinct from those in hepcidin transgenic mice.
authors.affiliation: Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Prince
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Langdon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Layman
authors.forename: Ian C
authors.initials: IC
authors.lastname: Prince
authors.forename: Miguel
authors.initials: M
authors.lastname: Sabogal
authors.forename: Howard H
authors.initials: HH
authors.lastname: Mak
authors.forename: Alan E
authors.initials: AE
authors.lastname: Berger
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Chrest
authors.forename: Qilu
authors.initials: Q
authors.lastname: Yu
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andrews
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Xue
authors.forename: Curt I
authors.initials: CI
authors.lastname: Civin
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: Cindy N
authors.initials: CN
authors.lastname: Roy
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D002908:Chronic Disease; D015672:Erythroid Precursor Cells / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis; D064451:Hepcidins; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood; D007509:Irritants / Q000009:adverse effects / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D014425:Turpentine / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D018836:Inflammation Mediators; D007509:Irritants; D014425:Turpentine