Biological Trace Element Research

, Volume 150, Issue 1–3, pp 314–321 | Cite as

Zinc Suppressed the Airway Inflammation in Asthmatic Rats: Effects of Zinc on Generation of Eotaxin, MCP-1, IL-8, IL-4, and IFN-γ

  • Hongyan Lu
  • Yue Xin
  • Yan Tang
  • Genbao Shao


Airway epithelium is rich in labile zinc (Zn), which may have an important protective role in the airway epithelium. The aim of this study is to investigate the effects of Zn on the airway inflammation and the generation of eotaxin, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-4 (IL-4), and interferon-γ (IFN-γ) in rat models of ovalbumin (OVA)-induced allergic airway inflammation. For this purpose, animal model of asthma was established by OVA challenge and zinc-deficient and zinc-supplemented diets were given. Thirty-two Sprague–Dawley rats were divided into four groups: zinc-deficient diet with OVA treatment group, zinc-supplemented diet with OVA treatment group, zinc-normal diet with OVA treatment group, and zinc-normal diet with saline treatment group. Twenty-four hours after asthma was induced, lung histomorphological changes, cells in bronchoalveolar lavage fluid (BALF), contents of eotaxin, MCP-1, and IL-8 in BALF, and the expression of IFN-γ and IL-4 mRNAs were observed. Compared with the group of zinc-normal diet with OVA challenge rats, the group of zinc-deficient rats had higher numbers of eosinophils, neutrophils, and monocytes in BALF, as well as higher contents of eotaxin and MCP-1 in BALF and lower expression of lung IFN-γ mRNA. Conversely, Zn supplementation would decrease the numbers of eosinophils, neutrophils, and monocytes in BALF; suppress eotaxin and MCP-1 protein secretion; and increase lung IFN-γ mRNA expression. No significant difference was observed in IL-8 and IL-4 among OVA-challenged rats with different zinc diets. These studies suggested that Zn may be an important anti-inflammatory mediator of airway inflammation.


Zinc Airway inflammation Eotaxin MCP-1 IL-8 IL-4 IFN-γ 



This research was supported by Natural Science Foundation of Jiangsu Province, China (BK2011485), the Social Development Foundation of Zhenjiang, China (SH2011022).


  1. 1.
    Murgia C, Grosser D, Truong-Tran AQ, Roscioli E, Michalczyk A, Ackland ML, Stoltenberg M, Danscher G, Lang C, Knight D, Perozzi G, Ruffin RE, Zalewski P (2011) Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation. Nutrients 3:910–928PubMedCrossRefGoogle Scholar
  2. 2.
    Zalewski PD, Truong-Tran AQ, Grosser D, Jayaram L, Murgia C, Ruffin RE (2005) Zinc metabolism in airway epithelium and airway inflammation: basic mechanisms and clinical targets. A review. Pharmacol Ther 105:127–149PubMedCrossRefGoogle Scholar
  3. 3.
    Carneiro MF, Rhoden CR, Amantéa SL, Barbosa F Jr (2011) Low concentrations of selenium and zinc in nails are associated with childhood asthma. Biol Trace Elem Res 144:244–252PubMedCrossRefGoogle Scholar
  4. 4.
    Haase H, Overbeck S, Rink L (2008) Zinc supplementation for the treatment or prevention of disease: current status and future perspectives. Exp Gerontol 43:394–408PubMedCrossRefGoogle Scholar
  5. 5.
    Nurmatov U, Devereux G, Sheikh A (2011) Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis. J Allergy Clin Immunol 127:724–733PubMedCrossRefGoogle Scholar
  6. 6.
    Morgan CI, Ledford JR, Zhou P, Page K (2008) Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen. Environ Health Perspect 116:826–831CrossRefGoogle Scholar
  7. 7.
    Danjo K, Takahashi I, Umeda T, Ando S, Itai K, Nakaji S (2010) Association between concentration of trace elements in serum and bronchial asthma among Japanese general population. J Trace Elem Med Biol 24:236–242PubMedCrossRefGoogle Scholar
  8. 8.
    Adamek-Guzik T, Czerniawska-Mysik G, Guzik T (1994) Bronchial asthma—a chronic inflammatory disorder. Int Arch Allergy Immunol 105:83–90CrossRefGoogle Scholar
  9. 9.
    Kung TT, Jones H, Adams GK, Umland SP, Kreutner W, Egan RW, Chapman RW, Watnick AS (2007) Characterization of a murine model of allergic pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 292:577–584Google Scholar
  10. 10.
    Shin YS, Takeda K, Gelfand EW (2009) Understanding asthma using animal models. Allergy Asthma Immunol Res 1:10–18PubMedCrossRefGoogle Scholar
  11. 11.
    Truong-Tran AQ, Ruffin RE, Foster PS, Koskinen AM, Coyle P, Philcox JC, Rofe AM, Zalewski PD (2002) Altered zinc homeostasis and caspase-3 activity in murine allergic airway inflammation. Am J Respir Cell Mol Biol 27:286–296PubMedGoogle Scholar
  12. 12.
    Feng L (2000) Role of chemokines in inflammation and immunoregulation. Immunol Res 21:203–210PubMedCrossRefGoogle Scholar
  13. 13.
    Bosnjak B, Stelzmueller B, Erb KJ, Epstein MM (2011) Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res 12:114PubMedCrossRefGoogle Scholar
  14. 14.
    Kahmann L, Uciechowski P, Warmuth S, Malavolta M, Mocchegiani E, Rink L (2006) Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. Biogerontology 7:429–435PubMedCrossRefGoogle Scholar
  15. 15.
    Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, Ruffin R, Zalewski P (2007) Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 292:577–584CrossRefGoogle Scholar
  16. 16.
    Lu HY, Mao XQ, Wen Y, Zhang L (2009) Suppresses airway inflammation in asthmatic rats through regulation of Th1/Th2 balance and activity. Basic Clin Med 29:531–534Google Scholar
  17. 17.
    Coyle P, Philcox JC, Rofe AM (1999) Metallothionein-null mice absorb less Zn from an egg-white diet, but a similar amount from solutions, although with altered intertissue Zn distribution. J Nutr 129:372–379PubMedGoogle Scholar
  18. 18.
    Verbanac D, Milin C, Domitrovic R, Giacometti J, Pantovic R, Ciganj Z (1997) Determination of standard zinc values in the intact tissues of mice by ICP spectrometry. Biol Trace Elem Res 57:91–96PubMedCrossRefGoogle Scholar
  19. 19.
    Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD (2001) New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol 79:170–177PubMedCrossRefGoogle Scholar
  20. 20.
    Truong-Tran AQ, Ho LH, Chai F, Zalewski PD (2000) Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell death. J Nutr 130(Suppl):1459–1466Google Scholar
  21. 21.
    Truong-Tran AQ, Grosser D, Ruffin RE, Murgia C, Zalewski PD (2002) Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation. Biochem Pharmacol 66:459–468Google Scholar
  22. 22.
    Clark K, Simson L, Newcombe N, Koskinen AM, Mattes J, Lee NA, Lee JJ, Dent LA, Matthaei KI, Foster PS (2004) Eosinophil degranulation in the allergic lung of mice primarily occurs in the airway lumen. J Leukoc Biol 75:1001–1009PubMedCrossRefGoogle Scholar
  23. 23.
    Taha RA, Minshall EM, Miotto D, Shimbara A, Luster A, Hogg JC, Hamid QA (1999) Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals. J Allergy Clin Immunol 103:476–483PubMedCrossRefGoogle Scholar
  24. 24.
    Richter M, Cantin AM, Beaulieu C, Cloutier A, Larivée P (2003) Zinc chelators inhibit eotaxin, RANTES, and MCP-1 production in stimulated human airway epithelium and fibroblasts. Am J Physiol Lung Cell Mol Physiol 285:719–729Google Scholar
  25. 25.
    Beck FW, Prasad AS, Kaplan J, Fitzgerald JT, Brewer GJ (1997) Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol 272:1002–1007Google Scholar
  26. 26.
    Prasad AS, Beck FWJ, Grabowski SM, Kaplan J, Mathog RH (1997) Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in non-cancer subjects. Proc Assoc Am Phys 109:68–77PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PediatricsThe Affiliated Hospital of Jiangsu UniversityZhenjiangChina
  2. 2.Department of Cell Biology, School of MedicineJiangsu UniversityZhenjiangChina

Personalised recommendations