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Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia

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Abstract

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

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References

  1. Weiss G (2002) Pathogenesis and treatment of anaemia of chronic disease. Blood Rev 16:87–96

    Article  PubMed  Google Scholar 

  2. Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352:1011–1023

    Article  CAS  PubMed  Google Scholar 

  3. Jurado RL (1997) Iron, infections, and anemia of inflammation. Clin Infect Dis 25:888–895

    Article  CAS  PubMed  Google Scholar 

  4. Brugnara C (2003) Iron deficiency and erythropoiesis: new diagnostic approaches. Clin Chem 49:1573–1578

    Article  CAS  PubMed  Google Scholar 

  5. Thomas C, Thomas L (2002) Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 48:1066–1076

    CAS  PubMed  Google Scholar 

  6. Metzgeroth G, Adelberger V, Dorn-Beineke A, Kuhn C, Schatz M, Maywald O, Bertsch T, Wisser H, Hehlmann R, Hastka J (2005) Soluble transferrin receptor and zinc protoporphyrin—competitors or efficient partners? Eur J Haematol 75:309–317

    Article  CAS  PubMed  Google Scholar 

  7. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781

    Article  CAS  PubMed  Google Scholar 

  8. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (2004) Il-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276

    CAS  PubMed  Google Scholar 

  9. Nemeth E, Ganz T (2006) Hepcidin and iron-loading anemias. Haematologica 91:727–732

    CAS  PubMed  Google Scholar 

  10. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093

    Article  CAS  PubMed  Google Scholar 

  11. Kemna EH, Tjalsma H, Willems HL, Swinkels DW (2008) Hepcidin: from discovery to differential diagnosis. Haematologica 93:90–97

    Article  CAS  PubMed  Google Scholar 

  12. Kemna EH, Tjalsma H, Podust VN, Swinkels DW (2007) Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 53:620–628

    Article  CAS  PubMed  Google Scholar 

  13. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T (2003) Hepcidin, a putative mediator of anemia of inflammation, is a type ii acute-phase protein. Blood 101:2461–2463

    Article  CAS  PubMed  Google Scholar 

  14. Piperno A, Mariani R, Trombini P, Girelli D (2009) Hepcidin modulation in human diseases: from research to clinic. World J Gastroenterol 15:538–551

    Article  CAS  PubMed  Google Scholar 

  15. Theurl I, Aigner E, Theurl M, Nairz M, Seifert M, Schroll A, Sonnweber T, Eberwein L, Witcher DR, Murphy AT, Wroblewski VJ, Wurz E, Datz C, Weiss G (2009) Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood 113:5277–5286

    Article  CAS  PubMed  Google Scholar 

  16. Barosi G (1994) Inadequate erythropoietin response to anemia: definition and clinical relevance. Ann Hematol 68:215–223

    Article  CAS  PubMed  Google Scholar 

  17. Ganz T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102:783–788

    Article  CAS  PubMed  Google Scholar 

  18. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S (2002) Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 99:4596–4601

    Article  CAS  PubMed  Google Scholar 

  19. Beutler E (2007) Iron storage disease: facts, fiction and progress. Blood Cells Mol Dis 39:140–147

    Article  CAS  PubMed  Google Scholar 

  20. Lee GR (1983) The anemia of chronic disease. Semin Hematol 20:61–80

    CAS  PubMed  Google Scholar 

  21. Dallalio G, Law E, Means RT Jr (2006) Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations. Blood 107:2702–2704

    Article  CAS  PubMed  Google Scholar 

  22. Fleming RE (2008) Iron and inflammation: cross-talk between pathways regulating hepcidin. J Mol Med 86:491–494

    Article  PubMed  Google Scholar 

  23. Ganz T (2006) Molecular pathogenesis of anemia of chronic disease. Pediatr Blood Cancer 46:554–557

    Article  PubMed  Google Scholar 

  24. De Domenico I, Ward DM, Kaplan J (2007) Hepcidin regulation: ironing out the details. J Clin Invest 117:1755–1758

    Article  PubMed  Google Scholar 

  25. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D (2005) Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with lps. Blood 106:1864–1866

    Article  CAS  PubMed  Google Scholar 

  26. Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (2006) Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood 107:4142–4148

    Article  CAS  PubMed  Google Scholar 

  27. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, Taube DH, Bloom SR, Tam FW, Chapman RS, Maxwell PH, Choi P (2009) Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease. Kidney Int 75:976–981

    Article  CAS  PubMed  Google Scholar 

  28. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037–1044

    CAS  PubMed  Google Scholar 

  29. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S (2006) Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108:3730–3735

    Article  CAS  PubMed  Google Scholar 

  30. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E (2007) Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 92:583–588

    Article  CAS  PubMed  Google Scholar 

  31. Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, Sakellaropoulos N, Papanikolaou G (2006) The effects of erythropoietic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 91:809–812

    CAS  PubMed  Google Scholar 

  32. Vokurka M, Krijt J, Sulc K, Necas E (2006) Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res 55:667–674

    CAS  PubMed  Google Scholar 

  33. Kanda J, Mizumoto C, Kawabata H, Tsuchida H, Tomosugi N, Matsuo K, Uchiyama T (2008) Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation. Haematologica 93:1550–1554

    Article  CAS  PubMed  Google Scholar 

  34. Nemeth E (2008) Iron regulation and erythropoiesis. Curr Opin Hematol 15:169–175

    Article  CAS  PubMed  Google Scholar 

  35. Pinto JP, Ribeiro S, Pontes H, Thowfeequ S, Tosh D, Carvalho F, Porto G (2008) Erythropoietin mediates hepcidin expression in hepatocytes through epor signaling and regulation of c/ebpalpha. Blood 111:5727–5733

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study were funded by Natural Science Foundation of Guangdong Province, China (NO 9151008901000043) and Science and Technology Board of Shantou City, China [NO (2008)085]. The assistance of central laboratory of Shantou University Medical College was gratefully acknowledged. We are much obliged to the staff and students working in Medical Examination Center of the first affiliated Hospital of Shantou University Medical College for their help in our study.

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Authors and Affiliations

  1. Department of Hemotology Laboratory, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, 515041, Shantou, Guangdong, China

    Pan-pan Cheng, Xiao-yang Jiao, Xue-hua Wang, Jing-hua Lin & Ying-mu Cai

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  1. Pan-pan Cheng
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  2. Xiao-yang Jiao
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  3. Xue-hua Wang
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  4. Jing-hua Lin
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  5. Ying-mu Cai
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Correspondence to Xiao-yang Jiao.

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Cheng, Pp., Jiao, Xy., Wang, Xh. et al. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. Clin Exp Med 11, 33–42 (2011). https://doi.org/10.1007/s10238-010-0102-9

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  • DOI: https://doi.org/10.1007/s10238-010-0102-9

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