title: Hepcidin is a key mediator of anemia of inflammation in Crohn's disease.
abstract: Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD.
  
  
  METHODS
  We enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin <12g/dL and <13.5g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded.
  
  
  RESULTS
  There was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r=0.853, p<0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r=0.723, p=0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r=0.546, p=0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r=0.528, p=0.029).
  
  
  CONCLUSIONS
  We demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.
authors.affiliation: Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Basseri
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Maria E
authors.initials: ME
authors.lastname: Vassilaki
authors.forename: Benjamin
authors.initials: B
authors.lastname: Basseri
authors.forename: Pedram
authors.initials: P
authors.lastname: Enayati
authors.forename: Omid
authors.initials: O
authors.lastname: Shaye
authors.forename: Leonidas A
authors.initials: LA
authors.lastname: Bourikas
authors.forename: Tom
authors.initials: T
authors.lastname: Ganz
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Papadakis
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000209:etiology / Q000652:urine; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood* / Q000150:complications / Q000652:urine; D005260:Female; D005293:Ferritins / Q000097:blood; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood* / Q000652:urine; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D064451:Hepcidins; D015850:Interleukin-6; D002097:C-Reactive Protein; D005293:Ferritins