Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation

Gaith Semrin, Douglas S. Fishman, Athos Bousvaros, Anna Zholudev, Andrew C. Saunders, Catherine E. Correia, Elizabeta Nemeth, Richard J. Grand, David A. Weinstein

Research output: Contribution to journalArticle

124 Citations (Scopus)

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 (Δ[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.

Original languageEnglish (US)
Pages (from-to)1101-1106
Number of pages6
JournalInflammatory Bowel Diseases
Volume12
Issue number12
DOIs
StatePublished - Dec 2006

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Intestinal Absorption
Crohn Disease
Iron
Inflammation
Interleukin-6
C-Reactive Protein
Hepcidins
Area Under Curve
Anemia
ferrous sulfate
Serum
Urine
Enterocytes
Blood Sedimentation
Hemoglobins
Eating
Biomarkers
Macrophages
Pediatrics
Cytokines

Keywords

  • Hepcidin
  • Inflammatory bowel disease
  • Interleukin-6
  • Pediatric

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation. / Semrin, Gaith; Fishman, Douglas S.; Bousvaros, Athos; Zholudev, Anna; Saunders, Andrew C.; Correia, Catherine E.; Nemeth, Elizabeta; Grand, Richard J.; Weinstein, David A.

In: Inflammatory Bowel Diseases, Vol. 12, No. 12, 12.2006, p. 1101-1106.

Research output: Contribution to journalArticle

Semrin, G, Fishman, DS, Bousvaros, A, Zholudev, A, Saunders, AC, Correia, CE, Nemeth, E, Grand, RJ & Weinstein, DA 2006, 'Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation', Inflammatory Bowel Diseases, vol. 12, no. 12, pp. 1101-1106. https://doi.org/10.1097/01.mib.0000235097.86360.04
Semrin, Gaith ; Fishman, Douglas S. ; Bousvaros, Athos ; Zholudev, Anna ; Saunders, Andrew C. ; Correia, Catherine E. ; Nemeth, Elizabeta ; Grand, Richard J. ; Weinstein, David A. / Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation. In: Inflammatory Bowel Diseases. 2006 ; Vol. 12, No. 12. pp. 1101-1106.
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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 (Δ[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.",
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AU - Semrin, Gaith

AU - Fishman, Douglas S.

AU - Bousvaros, Athos

AU - Zholudev, Anna

AU - Saunders, Andrew C.

AU - Correia, Catherine E.

AU - Nemeth, Elizabeta

AU - Grand, Richard J.

AU - Weinstein, David A.

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N2 - 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 (Δ[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.

AB - 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 (Δ[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.

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