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Iron Supplementation Attenuates the Inflammatory Status of Anemic Piglets by Regulating Hepcidin

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Abstract

Iron deficiency is common throughout the world and has been linked to immunity impairments. Using piglets to model human infants, we assessed the impact of systemic iron homeostasis on proinflammatory status. Artificially reared piglets were parenterally supplied with iron dextran by intramuscular administration at the age of 3 days. Relative to no iron supplementation (control), iron dextran-treated (FeDex) piglets increased hematological parameters as well as iron levels in serum and tissues from days 21 to 49. High expression of hepcidin was observed in FeDex-treated piglets, which correlated with suppressed expression of ferroportin in duodenum. Lower levels of proinflammatory cytokine (IL-6, TNF-α, IFN-γ, and IL-1β) transcripts were detected in ileum of FeDex-treated piglets, which indicated that iron supplementation could attenuate the increase of inflammatory cytokines caused by iron deficiency. Histopathological analysis of liver and duodenum proved the less inflammatory responses after iron supplementation. Hepcidin was highly stimulated by FeDex supplementation and attenuated the inflammation of anemia, which implied that hepcidin might had antiinflammatory function and is a candidate regulator of the cross-talk between iron regulation and inflammation.

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References

  1. Clark SF (2009) Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol 25:122–128

    Article  CAS  PubMed  Google Scholar 

  2. Svoboda M, Drabek J (2005) Iron deficiency in suckling piglets: etiology, clinical aspects and diagnosis. Folia Vet 49:104–111

    CAS  Google Scholar 

  3. Quintero-Gutierrez AG, Gonzalez-Rosendo G, Sanchez-Munoz J, Polo-Pozo J, Rodriguez-Jerez JJ (2008) Bioavailability of heme iron in biscuit filling suing piglets as an animal model for humans. Int J Biol Sci 4:58–62

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Egeli AK, Farmstadt T (1999) An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth. Res Vet Sci 66:179–184

    Article  CAS  PubMed  Google Scholar 

  5. Svoboda M, Drabek J (2007) Intramuscular versus subcutaneous administrationof iron dextran in suckling piglets. Acta Vet Brno 76:S11–S15

    Article  CAS  Google Scholar 

  6. Lipinski P, Starzynski RR, Canonne-Hergaux F et al (2010) Benefits and risks of iron supplementation in anemic neonatal pigs. Am J Pathol 177:1233–1243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. 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 

  8. Lee PL, Beutler E (2009) Regulation of hepcidin and iron overload disease. Annu Rev Pathol 4:489–515

    Article  CAS  PubMed  Google Scholar 

  9. Wrighting DM, Andrews NC (2006) Interleukin-6 induces hepcidin expression through STAT3. Blood 108:3204–3209

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Armitage AE, Eddowes LA, Gileadi U et al (2011) Hepcidin regulation by innate immune and infectious stimuli. Blood 118:4129–4139

    Article  PubMed  Google Scholar 

  11. Domeico ID, Zhang TY, Koening CL et al (2010) Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest 120:2395–2405

    Article  Google Scholar 

  12. Fielding J (1980) Methods Haematol 1:15–43

    CAS  Google Scholar 

  13. Torrance JD, Bothwell TH (1980) Tissue iron stores. In: Cook JD (ed) Methods in Hematology. Churchill Livingstone, New York, pp 90–115

    Google Scholar 

  14. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  15. Van Kempen G (1987) Avoid iron deficiency in piglets. Pigm 3:10–11

    Google Scholar 

  16. Wessling-Resnick M (2010) Iron homeostasis and the inflammatory response. Annu Rev Nutr 30:105–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. McDonald FF, Dunlop D, Bates CM (1955) An effective treatment for anemia of piglets. Br Vet J 111:403–404

    Google Scholar 

  18. Ku PK, Miller ER, Ullrey DE (1983) Effect of parenteraliron on serum electrolytes of the baby pig. J Anim Sci 57:638–644

    CAS  PubMed  Google Scholar 

  19. Park CH, Valore EV, Waring AJ, Ganz T (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810

    Article  CAS  PubMed  Google Scholar 

  20. Thomas C, Oates PS (2004) Ferroportin/IREG-1/MTP-1/SLC40A1 modulates the uptake of iron at the apical membrane of enterocytes. Gut 53:44–49

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Nemeth E, Rivera S, Gabayan V et al (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Pagani A, Nai A, Corna G et al (2011) Low hepcidin accounts for the proinflammatory status associated with iron deficiency. Blood 118(3):736–746

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 31272455) and Zhejiang Provincial Key Science and Technology Innovation Team (No. 2011R50025).

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No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. The work described was original research that has not been published previously and not under consideration for publication elsewhere.

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Correspondence to Huahua Du.

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Pu, Y., Guo, B., Liu, D. et al. Iron Supplementation Attenuates the Inflammatory Status of Anemic Piglets by Regulating Hepcidin. Biol Trace Elem Res 167, 28–35 (2015). https://doi.org/10.1007/s12011-015-0295-6

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  • DOI: https://doi.org/10.1007/s12011-015-0295-6

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