title: Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation.
abstract: BACKGROUND
  Anemia in patients with Crohn's disease (CD) is a common problem of multifactorial origin, including blood loss, malabsorption of iron, and anemia of inflammation. Anemia of inflammation is caused by the effects of inflammatory cytokines [predominantly interleukin-6 (IL-6)] on iron transport in enterocytes and macrophages. We sought to elucidate alterations in iron absorption in pediatric patients with active and inactive CD.
  
  
  METHODS
  Nineteen subjects with CD (8 female, 11 male patients) were recruited between April 2003 and June 2004. After an overnight fast, serum iron and hemoglobin levels, serum markers of inflammation [IL-6, C-reactive protein (CRP), and erythrocyte sedimentation rate], and a urine sample for hepcidin assay were obtained at 8 am. Ferrous sulfate (1 mg/kg) was administered orally, followed by determination of serum iron concentrations hourly for 4 hours after the ingestion of iron. An area under the curve for iron absorption was calculated for each patient data set.
  
  
  RESULTS
  There was a strong inverse correlation between the area under the curve and IL-6 (P = 0.002) and area under the curve and CRP levels (P = 0.04). Similarly, the difference between baseline and 2-hour serum iron level (Delta[Fe]2hr) correlated with IL-6 (P = 0.008) and CRP (P = 0.045). When cutoff values for IL-6 (>5 pg/mL) and CRP (>1.0 mg/dL) were used, urine hepcidin levels also positively correlated with IL-6 and CRP levels (P = 0.003 and 0.007, respectively).
  
  
  CONCLUSIONS
  Subjects with active CD have impaired oral iron absorption and elevated IL-6 levels compared with subjects with inactive disease. These findings suggest that oral iron may be of limited benefit to these patients. Future study is needed to define the molecular basis for impaired iron absorption.
authors.affiliation: Center for Inflammatory Bowel Disease and Divisions of Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Gaith
authors.initials: G
authors.lastname: Semrin
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Fishman
authors.forename: Athos
authors.initials: A
authors.lastname: Bousvaros
authors.forename: Anna
authors.initials: A
authors.lastname: Zholudev
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Saunders
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Correia
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Grand
authors.forename: David A
authors.initials: DA
authors.lastname: Weinstein
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002648:Child; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D003710:Demography; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008286:Malabsorption Syndromes / Q000473:pathology*; D008297:Male
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007501:Iron