Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection

Q. de Mast, B. Nadjm, H. Reyburn, E.H.J.M. Kemna, B. Amos, C.M.M. Laarakkers, S. Silalye, H. Verhoef, R.W. Sauerwein, D.W. Swinkels, A.J.A.M. van der Ven

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Abstract

Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone hepcidin in anemic Tanzanian children with febrile Plasmodium falciparum malaria. Before initiation of antimalarial treatment, urinary concentrations of hepcidin were strongly elevated and were associated with iron maldistribution, as was suggested by the presence of hypoferremia and high serum concentrations of ferritin. Antimalarial treatment resulted in a rapid decrease in urinary concentrations of hepcidin and reversal of the hypoferremia. Exploration of regulatory pathways of hepcidin production by analysis of iron, erythropoietic, and inflammatory indices suggested that reduced erythropoietic activity and inflammation stimulated hepcidin production. We conclude that high concentrations of hepcidin explain the observed disturbances in host iron homeostasis associated with malaria and may contribute to malarial anemia and an impaired erythropoietic response to iron supplementation
Original languageEnglish
Pages (from-to)253-262
JournalThe Journal of Infectious Diseases
Volume199
Issue number2
DOIs
Publication statusPublished - 2009

Fingerprint

Hepcidins
Homeostasis
Iron
Infection
Malaria
Antimalarials
Falciparum Malaria
Ferritins
Anemia
Fever
Therapeutics
Hormones
Inflammation

Keywords

  • plasmodium-falciparum malaria
  • soluble transferrin receptor
  • mass-spectrometry
  • anemia
  • serum
  • erythropoietin
  • ferroportin
  • expression
  • children
  • inflammation

Cite this

de Mast, Q., Nadjm, B., Reyburn, H., Kemna, E. H. J. M., Amos, B., Laarakkers, C. M. M., ... van der Ven, A. J. A. M. (2009). Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. The Journal of Infectious Diseases, 199(2), 253-262. https://doi.org/10.1086/595790
de Mast, Q. ; Nadjm, B. ; Reyburn, H. ; Kemna, E.H.J.M. ; Amos, B. ; Laarakkers, C.M.M. ; Silalye, S. ; Verhoef, H. ; Sauerwein, R.W. ; Swinkels, D.W. ; van der Ven, A.J.A.M. / Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. In: The Journal of Infectious Diseases. 2009 ; Vol. 199, No. 2. pp. 253-262.
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abstract = "Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone hepcidin in anemic Tanzanian children with febrile Plasmodium falciparum malaria. Before initiation of antimalarial treatment, urinary concentrations of hepcidin were strongly elevated and were associated with iron maldistribution, as was suggested by the presence of hypoferremia and high serum concentrations of ferritin. Antimalarial treatment resulted in a rapid decrease in urinary concentrations of hepcidin and reversal of the hypoferremia. Exploration of regulatory pathways of hepcidin production by analysis of iron, erythropoietic, and inflammatory indices suggested that reduced erythropoietic activity and inflammation stimulated hepcidin production. We conclude that high concentrations of hepcidin explain the observed disturbances in host iron homeostasis associated with malaria and may contribute to malarial anemia and an impaired erythropoietic response to iron supplementation",
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de Mast, Q, Nadjm, B, Reyburn, H, Kemna, EHJM, Amos, B, Laarakkers, CMM, Silalye, S, Verhoef, H, Sauerwein, RW, Swinkels, DW & van der Ven, AJAM 2009, 'Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection', The Journal of Infectious Diseases, vol. 199, no. 2, pp. 253-262. https://doi.org/10.1086/595790

Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. / de Mast, Q.; Nadjm, B.; Reyburn, H.; Kemna, E.H.J.M.; Amos, B.; Laarakkers, C.M.M.; Silalye, S.; Verhoef, H.; Sauerwein, R.W.; Swinkels, D.W.; van der Ven, A.J.A.M.

In: The Journal of Infectious Diseases, Vol. 199, No. 2, 2009, p. 253-262.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection

AU - de Mast, Q.

AU - Nadjm, B.

AU - Reyburn, H.

AU - Kemna, E.H.J.M.

AU - Amos, B.

AU - Laarakkers, C.M.M.

AU - Silalye, S.

AU - Verhoef, H.

AU - Sauerwein, R.W.

AU - Swinkels, D.W.

AU - van der Ven, A.J.A.M.

N1 - Online first

PY - 2009

Y1 - 2009

N2 - Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone hepcidin in anemic Tanzanian children with febrile Plasmodium falciparum malaria. Before initiation of antimalarial treatment, urinary concentrations of hepcidin were strongly elevated and were associated with iron maldistribution, as was suggested by the presence of hypoferremia and high serum concentrations of ferritin. Antimalarial treatment resulted in a rapid decrease in urinary concentrations of hepcidin and reversal of the hypoferremia. Exploration of regulatory pathways of hepcidin production by analysis of iron, erythropoietic, and inflammatory indices suggested that reduced erythropoietic activity and inflammation stimulated hepcidin production. We conclude that high concentrations of hepcidin explain the observed disturbances in host iron homeostasis associated with malaria and may contribute to malarial anemia and an impaired erythropoietic response to iron supplementation

AB - Disturbances in iron homeostasis are frequently observed in individuals with malaria. To study the effect of malaria and its treatment on iron homeostasis and to provide a mechanistic explanation for observed alterations in iron distribution, we studied the course of the iron regulatory hormone hepcidin in anemic Tanzanian children with febrile Plasmodium falciparum malaria. Before initiation of antimalarial treatment, urinary concentrations of hepcidin were strongly elevated and were associated with iron maldistribution, as was suggested by the presence of hypoferremia and high serum concentrations of ferritin. Antimalarial treatment resulted in a rapid decrease in urinary concentrations of hepcidin and reversal of the hypoferremia. Exploration of regulatory pathways of hepcidin production by analysis of iron, erythropoietic, and inflammatory indices suggested that reduced erythropoietic activity and inflammation stimulated hepcidin production. We conclude that high concentrations of hepcidin explain the observed disturbances in host iron homeostasis associated with malaria and may contribute to malarial anemia and an impaired erythropoietic response to iron supplementation

KW - plasmodium-falciparum malaria

KW - soluble transferrin receptor

KW - mass-spectrometry

KW - anemia

KW - serum

KW - erythropoietin

KW - ferroportin

KW - expression

KW - children

KW - inflammation

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DO - 10.1086/595790

M3 - Article

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SP - 253

EP - 262

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

SN - 0022-1899

IS - 2

ER -