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Zinc and the Immune System

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Nutrition and Immunity

Abstract

Zinc is an essential trace element that plays an important role in many physiological functions. One of the key functions of zinc is its influence on the immune system. Zinc is required for the development and functioning of immune cells in the innate and the adaptive immune system. Zinc homeostasis is finely controlled within each cell and any deregulation results in impairment of normal functions. Consequences of impaired homeostasis can be observed in many disease models such as infections, allergies, autoimmune diseases, and cancers. Zinc deficiency negatively influences the hematopoiesis and compromises the immune response at multiple molecular, cellular, and systemic levels. This chapter summarizes how zinc is involved in the immune system and how altered zinc levels within cells influence the immune response.

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References

  1. Prasad AS, Miale A Jr, Farid Z, et al. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypognadism. J Lab Clin Med. 1963;61:537–49.

    CAS  PubMed  Google Scholar 

  2. Rink L, Gabriel P. Zinc and the immune system. Proc Nutr Soc. 2000;59(4):541–52. https://doi.org/10.1017/S0029665100000781.

    Article  CAS  PubMed  Google Scholar 

  3. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008;14(5–6):353–7. https://doi.org/10.2119/2008-00033.Prasad.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Prasad AS. Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr. 2013;4(2):176–90. https://doi.org/10.3945/an.112.003210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447–63.

    Article  Google Scholar 

  6. Otten JJ, Hellwig JP, Meyers LD, editors. Dietary reference intakes: the essential guide to nutrient requirements. Washington, DC: The National Academies Press; 2006.

    Google Scholar 

  7. Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für Ernährung, Schweizerische Gesellschaft für Ernährungsforschung, Schweizerische Vereinigung für Ernährung. Referenzwerte für die Nährstoffzufuhr. Bonn, Germany; 2016.

    Google Scholar 

  8. WHO. Trace elements in human nutrition and health. Geneva: World Health Organization; 1996.

    Google Scholar 

  9. EFSA Panel on Dietetic Products Nutrition and Allergies. Scientific opinion on dietary reference values for zinc. EFSA J. 2014;12. https://doi.org/10.2903/j.efsa.2014.3844.

  10. National Institutes of Health. Zinc fact sheet for consumers. 2016. https://ods.od.nih.gov/pdf/factsheets/Zinc-Consumer.pdf.

  11. King JC, Brown KH, Gibson RS, et al. Biomarkers of nutrition for development (BOND)—zinc review. J Nutr. 2016. https://doi.org/10.3945/jn.115.220079.

    Article  PubMed  Google Scholar 

  12. Roohani N, Hurrell R, Kelishadi R, et al. Zinc and its importance for human health: an integrative review. J Res Med Sci. 2013;18(2):144–57.

    PubMed  PubMed Central  Google Scholar 

  13. Brieger A, Rink L. Zink und Immunfunktionen. Ernährung Medizin. 2010;25(04):156–60. https://doi.org/10.1055/s-0030-1255322.

    Article  CAS  Google Scholar 

  14. U.S. Department of Agriculture, Agricultural Research Service. 2011. USDA National Nutrient Database for Standard Reference (24).

    Google Scholar 

  15. World Health Organization. World health report: reducing risks, promoting healthy life. World health report, vol. 2002. Geneva: World Health Organization; 2002. p. 1020–3311.

    Google Scholar 

  16. Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976–1980). Am J Clin Nutr. 2003;78(4):756–64.

    Article  CAS  PubMed  Google Scholar 

  17. Oleske JM, Valentine JL, Minnefor AB. The effects of acute infection on blood lead, copper, and zinc levels in children. Health Lab Sci. 1975;12(3):230–3.

    CAS  PubMed  Google Scholar 

  18. Singh A, Smoak BL, Patterson KY, et al. Biochemical indices of selected trace minerals in men: effect of stress. Am J Clin Nutr. 1991;53(1):126–31.

    Article  CAS  PubMed  Google Scholar 

  19. Jain VK, Mohan G. Serum zinc and copper in myocardial infarction with particular reference to prognosis. Biol Trace Elem Res. 1991;31(3):317–22. https://doi.org/10.1007/BF02990200.

    Article  CAS  PubMed  Google Scholar 

  20. Lindeman RD, Baxter DJ, Yunice AA, et al. Serum concentrations and urinary excretions of zinc in cirrhosis, nephrotic syndrome and renal insufficiency. Am J Med Sci. 1978;275(1):17–31.

    Article  CAS  PubMed  Google Scholar 

  21. Hobisch-Hagen P, Mörtl M, Schobersberger W. Hemostatic disorders in pregnancy and the peripartum period. Acta Anaesthesiol Scand Suppl. 1997;111:216–7.

    CAS  PubMed  Google Scholar 

  22. Brown KH, Rivera JA, Bhutta Z, et al. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull. 2004;25(1 Suppl 2):S99–203.

    PubMed  Google Scholar 

  23. Jiang P, Guo Z. Fluorescent detection of zinc in biological systems: recent development on the design of chemosensors and biosensors. Coord Chem Rev. 2004;248(1):205–29. https://doi.org/10.1016/j.cct.2003.10.013.

    Article  CAS  Google Scholar 

  24. Haase H, Rink L. Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr. 2009;29:133–52. https://doi.org/10.1146/annurev-nutr-080508-141119.

    Article  CAS  PubMed  Google Scholar 

  25. Wellenreuther G, Cianci M, Tucoulou R, et al. The ligand environment of zinc stored in vesicles. Biochem Biophys Res Commun. 2009;380(1):198–203. https://doi.org/10.1016/j.bbrc.2009.01.074.

    Article  CAS  PubMed  Google Scholar 

  26. Kambe T, Hashimoto A, Fujimoto S. Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell Mol Life Sci. 2014;71(17):3281–95. https://doi.org/10.1007/s00018-014-1617-0.

    Article  CAS  PubMed  Google Scholar 

  27. Kimura T, Kambe T. The functions of metallothionein and ZIP and ZnT transporters: an overview and perspective. Int J Mol Sci. 2016;17(3). https://doi.org/10.3390/ijms17030336.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. King JC. Zinc: an essential but elusive nutrient. Am J Clin Nutr. 2011;94(2):679–84. https://doi.org/10.3945/ajcn.110.005744.

    Article  Google Scholar 

  29. Liu JZ, Jellbauer S, Poe AJ, et al. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe. 2012;11(3):227–39. https://doi.org/10.1016/j.chom.2012.01.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gilston BA, Skaar EP, Chazin WJ. Binding of transition metals to S100 proteins. Sci China Life Sci. 2016;59(8):792–801. https://doi.org/10.1007/s11427-016-5088-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mocchegiani E, Costarelli L, Giacconi R, et al. Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and immunosenescence. Exp Gerontol. 2006;41(11):1094–107. https://doi.org/10.1016/j.exger.2006.08.010.

    Article  CAS  PubMed  Google Scholar 

  32. Huang L, Tepaamorndech S. The SLC30 family of zinc transporters – a review of current understanding of their biological and pathophysiological roles. Mol Asp Med. 2013;34(2–3):548–60. https://doi.org/10.1016/j.mam.2012.05.008.

    Article  CAS  Google Scholar 

  33. Jeong J, Eide DJ. The SLC39 family of zinc transporters. Mol Asp Med. 2013;34(2–3):612–9. https://doi.org/10.1016/j.mam.2012.05.011.

    Article  CAS  Google Scholar 

  34. Kambe T, Tsuji T, Hashimoto A, et al. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol Rev. 2015;95(3):749–84. https://doi.org/10.1152/physrev.00035.2014.

    Article  CAS  PubMed  Google Scholar 

  35. Haase H, Rink L. Zinc signaling. In: Rink L, editor. Zinc in human health. Amsterdam: IOS Press; 2011. p. 94–117.

    Google Scholar 

  36. Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. 2017;9(12). https://doi.org/10.3390/nu9121286.

  37. Maywald M, Wessels I, Rink L. Zinc signals and immunity. Int J Mol Sci. 2017;18(10). https://doi.org/10.3390/ijms18102222.

    Article  PubMed Central  CAS  Google Scholar 

  38. Haase H, Rink L. Zinc signals and immune function. Biofactors. 2014;40(1):27–40. https://doi.org/10.1002/biof.1114.

    Article  CAS  PubMed  Google Scholar 

  39. Tartey S, Takeuchi O. Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol. 2017;36(2):57–73. https://doi.org/10.1080/08830185.2016.1261318.

    Article  CAS  PubMed  Google Scholar 

  40. Futosi K, Fodor S, Mócsai A. Reprint of Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol. 2013;17(4):1185–97. https://doi.org/10.1016/j.intimp.2013.11.010.

    Article  CAS  PubMed  Google Scholar 

  41. Fitzgerald KA, Rowe DC, Barnes BJ, et al. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med. 2003;198(7):1043–55. https://doi.org/10.1084/jem.20031023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hoebe K, Janssen EM, Kim SO, et al. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol. 2003;4(12):1223–9. https://doi.org/10.1038/ni1010.

    Article  CAS  PubMed  Google Scholar 

  43. Farlik M, Reutterer B, Schindler C, et al. Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity. 2010;33(1):25–34. https://doi.org/10.1016/j.immuni.2010.07.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gao JJ, Filla MB, Fultz MJ, et al. Autocrine/paracrine IFN-αβ mediates the lipopolysaccharide-induced activation of transcription factor Stat1α in mouse macrophages: pivotal role of Stat1α in induction of the inducible nitric oxide synthase gene. J Immunol. 1998;161(9):4803–10.

    CAS  PubMed  Google Scholar 

  45. Hill BG, Dranka BP, Bailey SM, et al. What part of NO Don’t you understand? Some answers to the cardinal questions in nitric oxide biology. J Biol Chem. 2010;285(26):19699–704. https://doi.org/10.1074/jbc.R110.101618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Brieger A, Rink L, Haase H. Differential regulation of TLR-dependent MyD88 and TRIF signaling pathways by free zinc ions. J Immunol. 2013;191(4):1808–17. https://doi.org/10.4049/jimmunol.1301261.

    Article  CAS  PubMed  Google Scholar 

  47. Graves JD, Krebs EG. Protein phosphorylation and signal transduction. Pharmacol Ther. 1999;82(2):111–21. https://doi.org/10.1016/S0163-7258(98)00056-4.

    Article  CAS  PubMed  Google Scholar 

  48. Haase H, Maret W. Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants. Biometals. 2005;18(4):333–8. https://doi.org/10.1007/s10534-005-3707-9.

    Article  CAS  PubMed  Google Scholar 

  49. Quest AF, Bloomenthal J, Bardes ES, et al. The regulatory domain of protein kinase C coordinates four atoms of zinc. J Biol Chem. 1992;267(14):10193–7.

    CAS  PubMed  Google Scholar 

  50. Beyersmann D, Haase H. Functions of zinc in signaling, proliferation and differentiation of mammalian cells. Biometals. 2001;14(3–4):331–41.

    Article  CAS  PubMed  Google Scholar 

  51. Zalewski PD, Forbes IJ, Giannakis C, et al. Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton. FEBS Lett. 1990;273(1–2):131–4. https://doi.org/10.1016/0014-5793(90)81067-X.

    Article  CAS  PubMed  Google Scholar 

  52. Jarosz M, Olbert M, Wyszogrodzka G, et al. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology. 2017;25(1):11–24. https://doi.org/10.1007/s10787-017-0309-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Perkins ND. Integrating cell-signalling pathways with NF-|[kappa]|B and IKK function. Nat Rev Mol Cell Biol. 2007;8(1):49–62. https://doi.org/10.1038/nrm2083.

    Article  CAS  PubMed  Google Scholar 

  54. Haase H, Ober-Blobaum JL, Engelhardt G, et al. Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes. J Immunol. 2008;181(9):6491–502.

    Article  CAS  PubMed  Google Scholar 

  55. Prasad AS, Bao B, Beck FWJ, et al. Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-κB. Nutrition. 2011;27(7–8):816–23. https://doi.org/10.1016/j.nut.2010.08.010.

    Article  CAS  PubMed  Google Scholar 

  56. Prasad AS, Bao B, Beck FWJ, et al. Antioxidant effect of zinc in humans. Free Radic Biol Med. 2004;37(8):1182–90. https://doi.org/10.1016/j.freeradbiomed.2004.07.007.

    Article  CAS  PubMed  Google Scholar 

  57. Bao B, Prasad AS, Beck FWJ, et al. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr. 2010;91(6):1634–41. https://doi.org/10.3945/ajcn.2009.28836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Amulic B, Cazalet C, Hayes GL, et al. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30(1):459–89. https://doi.org/10.1146/annurev-immunol-020711-074942.

    Article  CAS  PubMed  Google Scholar 

  59. Hasan R, Rink L, Haase H. Chelation of free Zn2+ impairs chemotaxis, phagocytosis, oxidative burst, degranulation, and cytokine production by neutrophil granulocytes. Biol Trace Elem Res. 2016;171(1):79–88. https://doi.org/10.1007/s12011-015-0515-0.

    Article  CAS  PubMed  Google Scholar 

  60. Hasan R, Rink L, Haase H. Zinc signals in neutrophil granulocytes are required for the formation of neutrophil extracellular traps. Innate Immun. 2013;19(3):253–64. https://doi.org/10.1177/1753425912458815.

    Article  CAS  PubMed  Google Scholar 

  61. Marreiro DDN, Cruz KJC, Morais JBS, et al. Zinc and oxidative stress: current mechanisms. Antioxidants. 2017;6(2):24. https://doi.org/10.3390/antiox6020024.

    Article  CAS  PubMed Central  Google Scholar 

  62. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84. https://doi.org/10.1016/j.biocel.2006.07.001.

    Article  CAS  PubMed  Google Scholar 

  63. Hasegawa H, Suzuki K, Nakaji S, et al. Effects of zinc on the reactive oxygen species generating capacity of human neutrophils and on the serum opsonic activity in vitro. Luminescence. 2000;15(5):321–7. https://doi.org/10.1002/1522-7243(200009/10)15:5<321:AID-BIO605>3.0.CO;2-O.

    Article  CAS  PubMed  Google Scholar 

  64. Driessen C, Hirv K, Rink L, et al. Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. Lymphokine Cytokine Res. 1994;13(1):15–20.

    CAS  PubMed  Google Scholar 

  65. Wellinghausen N, Driessen C, Rink L. Stimulation of human peripheral blood mononuclear cells by zinc and related cations. Cytokine. 1996;8(10):767–71. https://doi.org/10.1006/cyto.1996.0102.

    Article  CAS  PubMed  Google Scholar 

  66. Zhou Z, Wang L, Song Z, et al. Abrogation of nuclear factor-kappaB activation is involved in zinc inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha production and liver injury. Am J Pathol. 2004;164(5):1547–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bao B, Prasad AS, Beck FWJ, et al. Zinc modulates mRNA levels of cytokines. Am J Physiol Endocrinol Metab. 2003;285(5):E1095–102. https://doi.org/10.1152/ajpendo.00545.2002.

    Article  CAS  PubMed  Google Scholar 

  68. von Bulow V, Rink L, Haase H. Zinc-mediated inhibition of cyclic nucleotide phosphodiesterase activity and expression suppresses TNF- and IL-1 production in monocytes by elevation of Guanosine 3′,5′-cyclic monophosphate. J Immunol. 2005;175(7):4697–705. https://doi.org/10.4049/jimmunol.175.7.4697.

    Article  Google Scholar 

  69. Driessen C, Hirv K, Kirchner H, et al. Divergent effects of zinc on different bacterial pathogenic agents. J Infect Dis. 1995;171(2):486–9. https://doi.org/10.1093/infdis/171.2.486.

    Article  CAS  PubMed  Google Scholar 

  70. Von Bulow V, Dubben S, Engelhardt G, et al. Zinc-dependent suppression of TNF-alpha production is mediated by protein kinase A-induced inhibition of Raf-1, I kappa B kinase beta, and NF-kappa B. J Immunol. 2007;179(6):4180–6.

    Article  Google Scholar 

  71. Dubben S, Hönscheid A, Winkler K, et al. Cellular zinc homeostasis is a regulator in monocyte differentiation of HL-60 cells by 1 alpha,25-dihydroxyvitamin D3. J Leukoc Biol. 2010;87(5):833–44. https://doi.org/10.1189/jlb.0409241.

    Article  CAS  PubMed  Google Scholar 

  72. Rosenkranz E, Prasad AS, Rink L. Immunobiology and hematology of zinc. In: Rink L, editor. Zinc in human health. Amsterdam: IOS Press; 2011. p. 195–233.

    Google Scholar 

  73. Dierichs L, Kloubert V, Rink L. Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages. Eur J Nutr. 2017. https://doi.org/10.1007/s00394-017-1491-2.

    Article  PubMed  CAS  Google Scholar 

  74. Summersgill H, England H, Lopez-Castejon G, et al. Zinc depletion regulates the processing and secretion of IL-1β. Cell Death Dis. 2014;5:e1040. https://doi.org/10.1038/cddis.2013.547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sugiura T, Kuroda E, Yamashita U. Dysfunction of macrophages in metallothionein-knock out mice. J UOEH. 2004;26(2):193–205.

    Article  CAS  PubMed  Google Scholar 

  76. Kim Y-J, Kang J-H, Yang M-P. Zinc increases the phagocytic capacity of canine peripheral blood phagocytes in vitro. Vet Res Commun. 2009;33(3):251–61. https://doi.org/10.1007/s11259-008-9173-4.

    Article  PubMed  Google Scholar 

  77. Wan Y, Petris MJ, Peck SC. Separation of zinc-dependent and zinc-independent events during early LPS-stimulated TLR4 signaling in macrophage cells. FEBS Lett. 2014;588(17):2928–35. https://doi.org/10.1016/j.febslet.2014.05.043.

    Article  CAS  PubMed  Google Scholar 

  78. Cho J, Tsichlis PN. Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide. Proc Natl Acad Sci U S A. 2005;102(7):2350–5. https://doi.org/10.1073/pnas.0409856102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu M-J, Bao S, Galvez-Peralta M, et al. ZIP8 regulates host defense through zinc-mediated inhibition of NF-kappaB. Cell Rep. 2013;3(2):386–400. https://doi.org/10.1016/j.celrep.2013.01.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gao H, Zhao L, Wang H, et al. Metal transporter Slc39a10 regulates susceptibility to inflammatory stimuli by controlling macrophage survival. Proc Natl Acad Sci U S A. 2017;114(49):12940–5. https://doi.org/10.1073/pnas.1708018114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ho LH, Ruffin RE, Murgia C, et al. Labile zinc and zinc transporter ZnT4 in mast cell granules: role in regulation of caspase activation and NF-kappaB translocation. J Immunol. 2004;172(12):7750–60.

    Article  CAS  PubMed  Google Scholar 

  82. Kabu K, Yamasaki S, Kamimura D, et al. Zinc is required for Fc epsilon RI-mediated mast cell activation. J Immunol. 2006;177(2):1296–305.

    Article  CAS  PubMed  Google Scholar 

  83. Mandal A, Viswanathan C. Natural killer cells: in health and disease. Hematol Oncol Stem Cell Ther. 2015;8(2):47–55. https://doi.org/10.1016/j.hemonc.2014.11.006.

    Article  CAS  PubMed  Google Scholar 

  84. Allen JI, Perri RT, McClain CJ, et al. Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J Lab Clin Med. 1983;102(4):577–89.

    CAS  PubMed  Google Scholar 

  85. Tapazoglou E, Prasad AS, Hill G, et al. Decreased natural killer cell activity in patients with zinc deficiency with sickle cell disease. J Lab Clin Med. 1985;105(1):19–22.

    CAS  PubMed  Google Scholar 

  86. Metz CHD, Schroder AK, Overbeck S, et al. T-helper type 1 cytokine release is enhanced by in vitro zinc supplementation due to increased natural killer cells. Nutrition. 2007;23(2):157–63. https://doi.org/10.1016/j.nut.2006.10.007.

    Article  CAS  PubMed  Google Scholar 

  87. Muzzioli M, Stecconi R, Moresi R, et al. Zinc improves the development of human CD34+ cell progenitors towards NK cells and increases the expression of GATA-3 transcription factor in young and old ages. Biogerontology. 2009;10(5):593–604. https://doi.org/10.1007/s10522-008-9201-3.

    Article  CAS  PubMed  Google Scholar 

  88. Rajagopalan S, Winter CC, Wagtmann N, et al. The Ig-related killer cell inhibitory receptor binds zinc and requires zinc for recognition of HLA-C on target cells. J Immunol. 1995;155(9):4143–6.

    CAS  PubMed  Google Scholar 

  89. Vales-Gomez M, Erskine RA, Deacon MP, et al. The role of zinc in the binding of killer cell Ig-like receptors to class I MHC proteins. Proc Natl Acad Sci U S A. 2001;98(4):1734–9. https://doi.org/10.1073/pnas.041618298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Min W-P, Zhou D, Ichim TE, et al. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J Immunol. 2003;170(3):1304–12. https://doi.org/10.4049/jimmunol.170.3.1304.

    Article  CAS  PubMed  Google Scholar 

  91. Steinbrink K, Mahnke K, Grabbe S, et al. Myeloid dendritic cell: from sentinel of immunity to key player of peripheral tolerance? Hum Immunol. 2009;70(5):289–93. https://doi.org/10.1016/j.humimm.2009.02.003.

    Article  CAS  PubMed  Google Scholar 

  92. Kitamura H, Morikawa H, Kamon H, et al. Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol. 2006;7(9):971–7. https://doi.org/10.1038/ni1373.

    Article  CAS  PubMed  Google Scholar 

  93. Chow A, Toomre D, Garrett W, et al. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature. 2002;418(6901):988–94. https://doi.org/10.1038/nature01006.

    Article  CAS  PubMed  Google Scholar 

  94. Finamore A, Massimi M, Conti Devirgiliis L, et al. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J Nutr. 2008;138(9):1664–70.

    Article  CAS  PubMed  Google Scholar 

  95. Bao S, Knoell DL. Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1132–41. https://doi.org/10.1152/ajplung.00207.2006.

    Article  CAS  PubMed  Google Scholar 

  96. Heiliger E, Osmanagic A, Haase H, et al. N-cadherin-mediated cell adhesion is regulated by extracellular Zn2+. Metallomics. 2015;7(2):355–62. https://doi.org/10.1039/C4MT00300D.

    Article  CAS  PubMed  Google Scholar 

  97. Lansdown ABG, Mirastschijski U, Stubbs N, et al. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen. 2007;15(1):2–16. https://doi.org/10.1111/j.1524-475X.2006.00179.x.

    Article  PubMed  Google Scholar 

  98. Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28(3):321–6. https://doi.org/10.1007/s00268-003-7397-6.

    Article  PubMed  Google Scholar 

  99. Lu X, Wang M, Qi J, et al. Peptidoglycan recognition proteins are a new class of human bactericidal proteins. J Biol Chem. 2006;281(9):5895–907. https://doi.org/10.1074/jbc.M511631200.

    Article  CAS  PubMed  Google Scholar 

  100. Wang M, Liu L-H, Wang S, et al. Human peptidoglycan recognition proteins require zinc to kill both gram-positive and gram-negative bacteria and are synergistic with antibacterial peptides. J Immunol. 2007;178(5):3116–25. https://doi.org/10.4049/jimmunol.178.5.3116.

    Article  CAS  PubMed  Google Scholar 

  101. Haase H, Rink L. Multiple impacts of zinc on immune function. Metallomics. 2014;6(7):1175–80. https://doi.org/10.1039/c3mt00353a.

    Article  CAS  PubMed  Google Scholar 

  102. Hennigar SR, McClung JP. Nutritional immunity. Am J Lifestyle Med. 2016;10(3):170–3. https://doi.org/10.1177/1559827616629117.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Aydemir TB, Chang S-M, Guthrie GJ, et al. Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia). PLoS One. 2012;7(10):e48679. https://doi.org/10.1371/journal.pone.0048679.

    Article  CAS  PubMed  Google Scholar 

  104. Glaser R, Harder J, Lange H, et al. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol. 2005;6(1):57–64. https://doi.org/10.1038/ni1142.

    Article  CAS  PubMed  Google Scholar 

  105. Corbin BD, Seeley EH, Raab A, et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science. 2008;319(5865):962–5. https://doi.org/10.1126/science.1152449.

    Article  CAS  PubMed  Google Scholar 

  106. Subramanian Vignesh K, Landero Figueroa JA, Porollo A, et al. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity. 2013;39(4):697–710. https://doi.org/10.1016/j.immuni.2013.09.006.

    Article  CAS  PubMed  Google Scholar 

  107. Botella H, Stadthagen G, Lugo-Villarino G, et al. Metallobiology of host-pathogen interactions: an intoxicating new insight. Trends Microbiol. 2012;20(3):106–12. https://doi.org/10.1016/j.tim.2012.01.005.

    Article  CAS  PubMed  Google Scholar 

  108. Botella H, Peyron P, Levillain F, et al. Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe. 2011;10(3):248–59. https://doi.org/10.1016/j.chom.2011.08.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lappann M, Danhof S, Guenther F, et al. In vitro resistance mechanisms of Neisseria meningitidis against neutrophil extracellular traps. Mol Microbiol. 2013;89(3):433–49. https://doi.org/10.1111/mmi.12288.

    Article  CAS  PubMed  Google Scholar 

  110. Stork M, Grijpstra J, Bos MP, et al. Zinc piracy as a mechanism of Neisseria meningitidis for evasion of nutritional immunity. PLoS Pathog. 2013;9(10):e1003733. https://doi.org/10.1371/journal.ppat.1003733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bobrov AG, Kirillina O, Fetherston JD, et al. The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice. Mol Microbiol. 2014;93(4):759–75. https://doi.org/10.1111/mmi.12693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hoeger J, Simon T-P, Beeker T, et al. Persistent low serum zinc is associated with recurrent sepsis in critically ill patients – a pilot study. PLoS One. 2017;12(5):e0176069. https://doi.org/10.1371/journal.pone.0176069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hoeger J, Simon T-P, Doemming S, et al. Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis. Biometals. 2015;28(4):693–700. https://doi.org/10.1007/s10534-015-9858-4.

    Article  CAS  PubMed  Google Scholar 

  114. Nowak JE, Harmon K, Caldwell CC, et al. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr Crit Care Med. 2012;13(5):e323–9. https://doi.org/10.1097/PCC.0b013e31824fbd90.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Ganatra HA, Varisco BM, Harmon K, et al. Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis. Innate Immun. 2017;23(1):67–76. https://doi.org/10.1177/1753425916677073.

    Article  CAS  PubMed  Google Scholar 

  116. Wessels I, Cousins RJ. Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation. Am J Physiol Gastrointest Liver Physiol. 2015;309(9):G768–78. https://doi.org/10.1152/ajpgi.00179.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013;(6):CD001364. https://doi.org/10.1002/14651858.CD001364.pub4.

  118. Wang A, Huen SC, Luan HH, et al. Opposing effects of fasting metabolism on tissue tolerance in bacterial and viral inflammation. Cell. 2016;166(6):1512–1525.e12. https://doi.org/10.1016/j.cell.2016.07.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Raphael I, Nalawade S, Eagar TN, et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5–17. https://doi.org/10.1016/j.cyto.2014.09.011.

    Article  CAS  PubMed  Google Scholar 

  120. Schmitt N, Ueno H. Regulation of human helper T cell subset differentiation by cytokines. Curr Opin Immunol. 2015;34:130–6. https://doi.org/10.1016/j.coi.2015.03.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Golden MH, Jackson AA, Golden BE. Effect of zinc on thymus of recently malnourished children. Lancet. 1977;2(8047):1057–9.

    Article  CAS  PubMed  Google Scholar 

  122. Dowd PS, Kelleher J, Guillou PJ. T-lymphocyte subsets and interleukin-2 production in zinc-deficient rats. Br J Nutr. 1986;55(1):59–69.

    Article  CAS  PubMed  Google Scholar 

  123. DePasquale-Jardieu P, Fraker PJ. Further characterization of the role of corticosterone in the loss of humoral immunity in zinc-deficient A/J mice as determined by adrenalectomy. J Immunol. 1980;124(6):2650–5.

    CAS  PubMed  Google Scholar 

  124. King LE, Osati-Ashtiani F, Fraker PJ. Apoptosis plays a distinct role in the loss of precursor lymphocytes during zinc deficiency in mice. J Nutr. 2002;132(5):974–9.

    Article  CAS  PubMed  Google Scholar 

  125. Prasad AS, Meftah S, Abdallah J, et al. Serum thymulin in human zinc deficiency. J Clin Invest. 1988;82(4):1202–10. https://doi.org/10.1172/JCI113717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000;182(Suppl 1):S62–8. https://doi.org/10.1086/315916.

    Article  CAS  PubMed  Google Scholar 

  127. Bao B, Prasad AS, Beck FWJ, et al. Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells. Biochem Biophys Res Commun. 2011;407(4):703–7. https://doi.org/10.1016/j.bbrc.2011.03.084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Rosenkranz E, Metz CHD, Maywald M, et al. Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures. Mol Nutr Food Res. 2016;60. https://doi.org/10.1002/mnfr.201500524.

    Article  CAS  Google Scholar 

  129. Rosenkranz E, Hilgers R-D, Uciechowski P, et al. Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects. Eur J Nutr. 2017;56(2):557–67. https://doi.org/10.1007/s00394-015-1100-1.

    Article  CAS  PubMed  Google Scholar 

  130. Maywald M, Meurer SK, Weiskirchen R, et al. Zinc supplementation augments TGF-β1-dependent regulatory T cell induction. Mol Nutr Food Res. 2017;61(3). https://doi.org/10.1002/mnfr.201600493.

    Article  CAS  Google Scholar 

  131. Rosenkranz E, Maywald M, Hilgers R-D, et al. Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration. J Nutr Biochem. 2016;29:116–23. https://doi.org/10.1016/j.jnutbio.2015.11.010.

    Article  CAS  PubMed  Google Scholar 

  132. Maywald M, Wang F, Rink L. Zinc supplementation plays a crucial role in T helper 9 differentiation in allogeneic immune reactions and non-activated T cells. J Trace Elem Med Biol. 2018. https://doi.org/10.1016/j.jtemb.2018.02.004.

    Article  CAS  PubMed  Google Scholar 

  133. Beck FW, Kaplan J, Fine N, et al. Decreased expression of CD73 (ecto-5′-nucleotidase) in the CD8+ subset is associated with zinc deficiency in human patients. J Lab Clin Med. 1997;130(2):147–56.

    Article  CAS  PubMed  Google Scholar 

  134. Prasad AS. Zinc and immunity. Mol Cell Biochem. 1998;188(1–2):63–9.

    Article  CAS  PubMed  Google Scholar 

  135. Frost P, Rabbani P, Smith J, et al. Cell-mediated cytotoxicity and tumor growth in zinc-deficient mice. Proc Soc Exp Biol Med. 1981;167(3):333–7.

    Article  CAS  PubMed  Google Scholar 

  136. Fernandes G, Nair M, Onoe K, et al. Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice. Proc Natl Acad Sci U S A. 1979;76(1):457–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Kaltenberg J, Plum LM, Ober-Blöbaum JL, et al. Zinc signals promote IL-2-dependent proliferation of T cells. Eur J Immunol. 2010;40(5):1496–503. https://doi.org/10.1002/eji.200939574.

    Article  CAS  PubMed  Google Scholar 

  138. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010;33(2):153–65. https://doi.org/10.1016/j.immuni.2010.08.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Plum LM, Brieger A, Engelhardt G, et al. PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation. Metallomics. 2014;6(7):1277–87. https://doi.org/10.1039/c3mt00197k.

    Article  CAS  PubMed  Google Scholar 

  140. Palacios EH, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene. 2004;23(48):7990–8000. https://doi.org/10.1038/sj.onc.1208074.

    Article  CAS  PubMed  Google Scholar 

  141. Yu M, Lee W-W, Tomar D, et al. Regulation of T cell receptor signaling by activation-induced zinc influx. J Exp Med. 2011;208(4):775–85. https://doi.org/10.1084/jem.20100031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Aydemir TB, Liuzzi JP, McClellan S, et al. Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-gamma expression in activated human T cells. J Leukoc Biol. 2009;86(2):337–48. https://doi.org/10.1189/jlb.1208759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Osati-Ashtiani F, King LE, Fraker PJ. Variance in the resistance of murine early bone marrow B cells to a deficiency in zinc. Immunology. 1998;94(1):94–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Hojyo S, Miyai T, Fujishiro H, et al. Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. Proc Natl Acad Sci U S A. 2014;111(32):11786–91. https://doi.org/10.1073/pnas.1323557111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gruber K, Maywald M, Rosenkranz E, et al. Zinc deficiency adversely influences interleukin-4 and interleukin-6 signaling. J Biol Regul Homeost Agents. 2013;27(3):661–71.

    CAS  PubMed  Google Scholar 

  146. Strand TA, Hollingshead SK, Julshamn K, et al. Effects of zinc deficiency and pneumococcal surface protein A immunization on zinc status and the risk of severe infection in mice. Infect Immun. 2003;71(4):2009–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Kreft B, Fischer A, Krüger S, et al. The impaired immune response to diphtheria vaccination in elderly chronic hemodialysis patients is related to zinc deficiency. Biogerontology. 2000;1(1):61–6.

    Article  CAS  PubMed  Google Scholar 

  148. Albert MJ, Qadri F, Wahed MA, et al. Supplementation with zinc, but not vitamin A, improves seroconversion to vibriocidal antibody in children given an oral cholera vaccine. J Infect Dis. 2003;187(6):909–13. https://doi.org/10.1086/368132.

    Article  CAS  PubMed  Google Scholar 

  149. Hodkinson CF, Kelly M, Alexander HD, et al. Effect of zinc supplementation on the immune status of healthy older individuals aged 55–70 years: the ZENITH study. J Gerontol A Biol Sci Med Sci. 2007;62(6):598–608.

    Article  PubMed  Google Scholar 

  150. Mocchegiani E, Malavolta M. Zinc and aging. In: Rink L, editor. Zinc in human health. Amsterdam: IOS Press; 2011. p. 325–46.

    Google Scholar 

  151. Alam AN, Sarker SA, Wahed MA, et al. Enteric protein loss and intestinal permeability changes in children during acute shigellosis and after recovery: effect of zinc supplementation. Gut. 1994;35(12):1707–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Moroni F, Di Paolo ML, Rigo A, et al. Interrelationship among neutrophil efficiency, inflammation, antioxidant activity and zinc pool in very old age. Biogerontology. 2005;6(4):271–81. https://doi.org/10.1007/s10522-005-2625-0.

    Article  CAS  PubMed  Google Scholar 

  153. Fülöp T, Fouquet C, Allaire P, et al. Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev. 1997;96(1–3):15–34.

    Article  PubMed  Google Scholar 

  154. Butcher SK, Chahal H, Nayak L, et al. Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol. 2001;70(6):881–6.

    CAS  PubMed  Google Scholar 

  155. Kloubert V, Rink L. Zinc as a micronutrient and its preventive role of oxidative damage in cells. Food Funct. 2015;6(10):3195–204. https://doi.org/10.1039/C5FO00630A.

    Article  CAS  PubMed  Google Scholar 

  156. Cakman I, Rohwer J, Schütz RM, et al. Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mech Ageing Dev. 1996;87(3):197–209.

    Article  CAS  PubMed  Google Scholar 

  157. Paganelli R, Quinti I, Fagiolo U, et al. Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. Clin Exp Immunol. 1992;90(2):351–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Kahmann L, Uciechowski P, Warmuth S, et al. Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res. 2008;11(1):227–37. https://doi.org/10.1089/rej.2007.0613.

    Article  CAS  PubMed  Google Scholar 

  159. Duchateau J, Delepesse G, Vrijens R, et al. Beneficial effects of oral zinc supplementation on the immune response of old people. Am J Med. 1981;70(5):1001–4. https://doi.org/10.1016/0002-9343(81)90849-4.

    Article  CAS  PubMed  Google Scholar 

  160. Prasad AS, Beck FWJ, Bao B, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85(3):837–44.

    Article  CAS  PubMed  Google Scholar 

  161. Mocchegiani E, Muzzioli M, Giacconi R, et al. Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply. Mech Ageing Dev. 2003;124(4):459–68.

    Article  CAS  PubMed  Google Scholar 

  162. World Health Organization. The top 10 causes of death. 2017. http://www.who.int/mediacentre/factsheets/fs310/en/.

  163. World Health Organisation. Diarrhoeal disease. 2017. http://www.who.int/mediacentre/factsheets/fs330/en/.

  164. Haase H, Mocchegiani E, Rink L. Correlation between zinc status and immune function in the elderly. Biogerontology. 2006;7(5–6):421–8. https://doi.org/10.1007/s10522-006-9057-3.

    Article  CAS  PubMed  Google Scholar 

  165. Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc. 2004;44(5):594–603.

    Article  Google Scholar 

  166. Baum MK, Lai S, Sales S, et al. Randomized controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-positive adults. Clin Infect Dis. 2010;50(12):1653–60. https://doi.org/10.1086/652864.

    Article  CAS  PubMed  Google Scholar 

  167. Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Lancet. 2005;366(9500):1862–7. https://doi.org/10.1016/S0140-6736(05)67756-2.

    Article  CAS  PubMed  Google Scholar 

  168. Lodha R, Shah N, Mohari N, et al. Immunologic effect of zinc supplementation in HIV-infected children receiving highly active antiretroviral therapy: a randomized, double-blind, placebo-controlled trial. J Acquir Immune Defic Syndr. 2014;66(4):386–92. https://doi.org/10.1097/QAI.0000000000000191.

    Article  CAS  PubMed  Google Scholar 

  169. Asdamongkol N, Phanachet P, Sungkanuparph S. Low plasma zinc levels and immunological responses to zinc supplementation in HIV-infected patients with immunological discordance after antiretroviral therapy. Jpn J Infect Dis. 2013;66(6):469–74. https://doi.org/10.7883/yoken.66.469.

    Article  PubMed  Google Scholar 

  170. Mocchegiani E, Veccia S, Ancarani F, et al. Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS. Int J Immunopharmacol. 1995;17(9):719–27.

    Article  CAS  PubMed  Google Scholar 

  171. Green JA, Lewin SR, Wightman F, et al. A randomised controlled trial of oral zinc on the immune response to tuberculosis in HIV-infected patients. Int J Tuberc Lung Dis. 2005;9(12):1378–84.

    CAS  PubMed  Google Scholar 

  172. Fawzi WW, Villamor E, Msamanga GI, et al. Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania. Am J Clin Nutr. 2005;81(1):161–7.

    Article  CAS  PubMed  Google Scholar 

  173. Deloria-Knoll M, Steinhoff M, Semba RD, et al. Effect of zinc and vitamin A supplementation on antibody responses to a pneumococcal conjugate vaccine in HIV-positive injection drug users: a randomized trial. Vaccine. 2006;24(10):1670–9. https://doi.org/10.1016/j.vaccine.2005.09.047.

    Article  CAS  PubMed  Google Scholar 

  174. Kawaguchi T, Nagao Y, Abe K, et al. Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: a multicenter randomized controlled trial. Mol Med Rep. 2015;11(3):2159–66.

    Article  CAS  PubMed  Google Scholar 

  175. Murakami Y, Koyabu T, Kawashima A, et al. Zinc supplementation prevents the increase of transaminase in chronic hepatitis C patients during combination therapy with pegylated interferon alpha-2b and ribavirin. J Nutr Sci Vitaminol (Tokyo). 2007;53(3):213–8.

    Article  CAS  Google Scholar 

  176. Ko W-S, Guo C-H, Hsu G-SW, et al. The effect of zinc supplementation on the treatment of chronic hepatitis C patients with interferon and ribavirin. Clin Biochem. 2005;38(7):614–20. https://doi.org/10.1016/j.clinbiochem.2005.04.003.

    Article  CAS  PubMed  Google Scholar 

  177. Takagi H, Nagamine T, Abe T, et al. Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C. J Viral Hepat. 2001;8(5):367–71.

    Article  CAS  PubMed  Google Scholar 

  178. Hoque KM, Binder HJ. Zinc in the treatment of acute diarrhea: current status and assessment. Gastroenterology. 2006;130(7):2201–5. https://doi.org/10.1053/j.gastro.2006.02.062.

    Article  CAS  PubMed  Google Scholar 

  179. Malik A, Taneja DK, Devasenapathy N, et al. Zinc supplementation for prevention of acute respiratory infections in infants: a randomized controlled trial. Indian Pediatr. 2014;51(10):780–4.

    Article  PubMed  Google Scholar 

  180. Shah UH, Abu-Shaheen AK, Malik MA, et al. The efficacy of zinc supplementation in young children with acute lower respiratory infections: a randomized double-blind controlled trial. Clin Nutr. 2013;32(2):193–9. https://doi.org/10.1016/j.clnu.2012.08.018.

    Article  CAS  PubMed  Google Scholar 

  181. Sazawal S, Black RE, Jalla S, et al. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998;102(1 Pt 1):1–5.

    Article  CAS  PubMed  Google Scholar 

  182. Martinez-Estevez NS, Alvarez-Guevara AN, Rodriguez-Martinez CE. Effects of zinc supplementation in the prevention of respiratory tract infections and diarrheal disease in Colombian children: a 12-month randomised controlled trial. Allergol Immunopathol. 2016;44(4):368–75. https://doi.org/10.1016/j.aller.2015.12.006.

    Article  CAS  Google Scholar 

  183. Mahalanabis D, Lahiri M, Paul D, et al. Randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc or vitamin A in infants and young children with severe acute lower respiratory infection. Am J Clin Nutr. 2004;79(3):430–6.

    Article  CAS  PubMed  Google Scholar 

  184. Karyadi E, West CE, Schultink W, et al. A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr. 2002;75(4):720–7.

    Article  CAS  PubMed  Google Scholar 

  185. Mathur NK, Bumb RA, Mangal HN. Oral zinc in recurrent erythema nodosum leprosum reaction. Lepr India. 1983;55(3):547–52.

    CAS  PubMed  Google Scholar 

  186. Mathur NK, Bumb RA, Mangal HN, et al. Oral zinc as an adjunct to dapsone in lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1984;52(3):331–8.

    CAS  PubMed  Google Scholar 

  187. Mahajan PM, Jadhav VH, Patki AH, et al. Oral zinc therapy in recurrent erythema nodosum leprosum: a clinical study. Indian J Lepr. 1994;66(1):51–7.

    CAS  PubMed  Google Scholar 

  188. El-Shafei MM, Kamal AA, Soliman H, et al. Effect of oral zinc supplementation on the cell mediated immunity in lepromatous leprosy. J Egypt Public Health Assoc. 1988;63(5–6):311–36.

    CAS  PubMed  Google Scholar 

  189. Raqib R, Roy SK, Rahman MJ, et al. Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis. Am J Clin Nutr. 2004;79(3):444–50.

    Article  CAS  PubMed  Google Scholar 

  190. Rahman MJ, Sarker P, Roy SK, et al. Effects of zinc supplementation as adjunct therapy on the systemic immune responses in shigellosis. Am J Clin Nutr. 2005;81(2):495–502.

    Article  CAS  PubMed  Google Scholar 

  191. Roy SK, Raqib R, Khatun W, et al. Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh. Eur J Clin Nutr. 2008;62(7):849–55. https://doi.org/10.1038/sj.ejcn.1602795.

    Article  CAS  PubMed  Google Scholar 

  192. Zeba AN, Sorgho H, Rouamba N, et al. Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial. Nutr J. 2008;7:7. https://doi.org/10.1186/1475-2891-7-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Muller O, Becher H, van Zweeden AB, et al. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ. 2001;322(7302):1567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Shankar AH, Genton B, Baisor M, et al. The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. Am J Trop Med Hyg. 2000;62(6):663–9.

    Article  CAS  PubMed  Google Scholar 

  195. Richard SA, Zavaleta N, Caulfield LE, et al. Zinc and iron supplementation and malaria, diarrhea, and respiratory infections in children in the Peruvian Amazon. Am J Trop Med Hyg. 2006;75(1):126–32.

    Article  CAS  PubMed  Google Scholar 

  196. Bates CJ, Evans PH, Dardenne M, et al. A trial of zinc supplementation in young rural Gambian children. Br J Nutr. 1993;69(1):243–55.

    Article  CAS  PubMed  Google Scholar 

  197. Zinc Against Plasmodium Study Group. Effect of zinc on the treatment of Plasmodium falciparum malaria in children: a randomized controlled trial. Am J Clin Nutr. 2002;76(4):805–12.

    Article  Google Scholar 

  198. Sharquie KE, Najim RA, Farjou IB, et al. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clin Exp Dermatol. 2001;26(1):21–6.

    Article  CAS  PubMed  Google Scholar 

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    Nour Zahi Gammoh & Lothar Rink

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    Nima Rezaei

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Gammoh, N.Z., Rink, L. (2019). Zinc and the Immune System. In: Mahmoudi, M., Rezaei, N. (eds) Nutrition and Immunity. Springer, Cham. https://doi.org/10.1007/978-3-030-16073-9_8

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