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Zinc and the immune system

Published online by Cambridge University Press:  28 February 2007

Lothar Rink*
Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Ratzeburger Allee 160, D-23538 Lübeck, Germany
Corresponding Author: Dr Lothar Rink, fax +49 451 500 3069, email
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Zn is an essential trace element for all organisms. In human subjects body growth and development is strictly dependent on Zn. The nervous, reproductive and immune systems are particularly influenced by Zn deficiency, as well as by increased levels of Zn. The relationship between Zn and the immune system is complex, since there are four different types of influence associated with Zn. (1) The dietary intake and the resorption of Zn depends on the composition of the diet and also on age and disease status. (2) Zn is a cofactor in more than 300 enzymes influencing various organ functions having a secondary effect on the immune system. (3) Direct effects of Zn on the production, maturation and function of leucocytes. (4) Zn influences the function of immunostimulants used in the experimental systems. Here we summarize all four types of influence on the immune function. Nutritional aspects of Zn, the physiology of Zn, the influence of Zn on enzymes and cellular functions, direct effects of Zn on leucocytes at the cellular and molecular level, Zn-altered function of immunostimulants and the therapeutic use of Zn will be discussed in detail.

Meeting Report
Copyright © The Nutrition Society 2000


aCampo, C, Wellinghausen, N, Faber, C, Fischer, A & Rink, L (2000) Zinc inhibits the mixed lymphocyte culture. Biological Trace Element Research (In the Press).Google Scholar
Aicher, WK, Heer, AH, Trabandt, A, Bridges, SL Jr, Schroeder, HW Jr, Stransky, G, Gay, RE, Eibel, H, Peter, HH, Siebenlist, U, Koopman, WJ & Gay, S (1994) Overexpression of zinc-finger transcription factor z-225/Egr-1 in synoviocytes from rheumatoid arthritis patients. Journal of Immunology 152, 59405948.Google ScholarPubMed
Aicher, WK, Sakamoto, KM, Hack, A & Eibel, H (1999) Analysis of functional elements in the human Egr-1 gene promoter. Rheumatology International 8, 207214.CrossRefGoogle Scholar
Allen, JI, Perri, RT, McClain, CJ & Kay, NE (1983) Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. Journal of Laboratory and Clinical Medicine 102, 577589.Google ScholarPubMed
Andres, ME, Burger, C, Peral-Rubio, MJ, Battaglioli, E, Anderson, ME, Grimes, J, Dallman, J, Ballas, N & Mandel, G (1999) CoREST: a functional corepressor required for regulation of neural-specific gene expression. Proceedings of the National Academy of Sciences USA 96, 98739878.CrossRefGoogle ScholarPubMed
Antonucci, A, Di-Baldassarre, A, Di-Giacomo, F, Stuppia, L & Palka, G (1997) Detection of apoptosis in peripheral blood cells of 31 subjects affected by Down syndrome before and after zinc therapy. Ultrastructural Pathology 21, 449452.CrossRefGoogle ScholarPubMed
Armstrong, RC, Kim, JG & Hudson, LD (1995) Expression of myelin transcription factor I (MyTI), a 'zinc-finger' DNA-binding protein, in developing oligodendrocytes. Glia 14, 303321.CrossRefGoogle Scholar
Bach, JF (1981) The multi-faceted zinc dependency of the immune system. Immunology Today 4, 225227.CrossRefGoogle Scholar
Bach, JF (1983) Thymulin (FTS-Zn). Clinics in Immunology and Allergy 3, 133150.Google Scholar
Balaban, N, Goldkorn, T, Nhan, RT, Dang, LB, Scott, S, Ridgley, RM, Rasooly, A, Wright, SC, Larrick, JW, Rasooly, R & Carlson, JR (1998) Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280, 438440.CrossRefGoogle ScholarPubMed
Balaban, N & Novick, RP (1995) Autocrine regulation of toxin synthesis by Staphylococcus aureus. Proceedings of the National Academy of Sciences USA 92, 16191623.CrossRefGoogle ScholarPubMed
Bedwal, RS & Bahuguna, A (1994) Zinc, copper and selenium in reproduction. Experientia 50, 626640.CrossRefGoogle ScholarPubMed
Bentley, PJ (1992) Influx of zinc by channel catfish (Ictalurus punctatus): uptake from external environmental solutions. Comparative Biochemistry and Physiology 101C, 215217.Google Scholar
Berger, NA & Skinner, M (1974) Characterization of lymphocyte transformation induced by zinc ions. Journal of Cellular Biology 61, 4555.CrossRefGoogle ScholarPubMed
Bernatchez, C, Al-Daccak, R, Mayer, PE, Mehindate, K, Rink, L, Mecheri, S & Mourad, W (1997) Functional analysis of Mycoplasma arthritidis-derived mitogen interaction with class II molecules. Infection and Immunity 65, 20002005.Google ScholarPubMed
Bettger, WJ & O'Dell, BL (1993) Physiological roles of zinc in the plasma membrane of mammalian cells. Journal of Nutritional Biochemistry 4, 194207.CrossRefGoogle Scholar
Bonomini, M, Di Paolo, B, De Risio, F, Niri, L, Klinkmann, H, Ivanowich, P & Albertazzi, A (1993) Effects of zinc supplementation in chronic haemodialysis patients. Nephrology Dialysis and Transplantation 8, 11661168.Google ScholarPubMed
Braunschweig, CL, Sowers, M, Kovacevich, DS, Hill, GM & August, DA (1997) Parenteral zinc supplementation in adult humans during the acute phase response increases the febrile response. Journal of Nutrition 127, 7074.CrossRefGoogle ScholarPubMed
Brewer, GJ, Aster, JC, Knutsen, CA & Kruckeberg, WC (1979) Zinc inhibition of calmodulin: a proposed molecular mechanism of zinc action on cellular functions. American Journal of Hematology 7, 5360.CrossRefGoogle ScholarPubMed
Brewer, GJ & Bereza, UL (1982) Therapy of sickle cell anemia with membrane expander/calmodulin inhibitor classes of drugs. In Clinical, Biochemical, and Nutritional Aspects of Trace Elements, pp. 211220 [Prasad, AS, editor]. New York: Liss.Google Scholar
Brewer, GJ, Dick, RD, Yuzbasiyan-Gurkan, V, Johnson, V & Wang, Y (1994) Treatment of Wilson's disease with zinc. XIII: Therapy with zinc in presymptomatic patients from the time of diagnosis. Journal of Laboratory and Clinical Medicine 123, 849858.Google ScholarPubMed
Brewer, GJ & Yuzbasiyan-Gurkan, V (1992) Wilson disease. Medicine 71, 139164.CrossRefGoogle ScholarPubMed
Brignola, C, Belloli, C, DeSimone, G, Evangelisti, A, Parente, R, Mancini, R, Innan, P, Mocchegiani, E, Fabris, N & Morini, MC (1993) Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. Alimentary and Pharmacology and Therapeutics 7, 275280.CrossRefGoogle ScholarPubMed
Brodersen, HP, Holtkamp, W, Larbig, D, Beckers, B, Thiery, J, Lautenschlager, J, Probst, HJ, Ropertz, S & Yavari, A (1995) Zinc supplementation and hepatitis B vaccination in chronic haemodialysis patients a multicentre study. Nephrology Dialysis Transplantation 10, 1780.Google ScholarPubMed
Bulgarini, D, Habetswallner, D, Boccoli, G, Montesoro, E, Camagna, A, Mastroberardino, G, Rosania, C, Testa, U & Peschle, C (1989) Zinc modulates the mitogenic activation of human peripheral blood lymphocytes. Annali dell Istituto Superiore di Sanita 25, 463470.Google ScholarPubMed
Cakman, I, Kirchner, H & Rink, L (1997) Zinc supplementation reconstitutes the production of interferon-α by leukocytes from elderly persons. Journal of Interferon and Cytokine Research 17, 469472.CrossRefGoogle ScholarPubMed
Cakman, I, Rohwer, J, Schütz, RM, Kirchner, H & Rink, L (1996) Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mechanisms of Ageing and Development 87, 197209.CrossRefGoogle ScholarPubMed
Chalaux, E, Lopez-Rovira, T, Rosa, JL, Pons, G, Boxer, LM, Batrons, R & Ventura, F (1999) A zinc-finger transcription factor induced by TGF-beta promotes apoptotic cell death in epithelial Mv1Lu cells. FEBS Letters 457, 478482.CrossRefGoogle ScholarPubMed
Chandra, RK (1984) Excessive intake of zinc impairs immune responses. Journal of the American Medical Association 252, 14431446.CrossRefGoogle ScholarPubMed
Chang, CC, Ye, BH, Chaganti, RS & Dalla-Favera, R (1996) BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proceedings of the National Academy of Sciences USA 93, 69476952.CrossRefGoogle ScholarPubMed
Chavakis, T, May, AE, Preissner, KT & Kanse, SM (1999) Molecular mechanisms of zinc-dependent leukocyte adhesion involving the urokinase receptor and β2-integrins. Blood 93, 29762983.Google ScholarPubMed
Chesters, JK (1992) Trace elements–gene interactions. Nutrition Reviews 50, 217223.CrossRefGoogle Scholar
Chvapil, M (1976) Effect of zinc on cells and biomembranes. Medical Clinics of North America 60, 799812.CrossRefGoogle ScholarPubMed
Clohessy, PA & Golden, BE (1995) Calprotectin-mediated zinc chelation as a biostatic mechanism in host defense. Scandinavian Journal of Immunology 42, 551556.CrossRefGoogle Scholar
Coleman, JE (1992 a) Zinc proteins: Enzymes, storage proteins, transcription factors and replication proteins. Annual Review of Biochemistry 16, 897946.CrossRefGoogle Scholar
Coleman, JE (1992 b) Structure and mechanism of alkaline phosphatase. Annual Review of Biophysics and Biomolecular Structure 21, 441483.CrossRefGoogle ScholarPubMed
Coto, JA, Hadden, EM, Sauro, M, Zorn, N & Hadden, JW (1992) Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C. Proceedings of the National Academy of Sciences USA 89, 77527756.CrossRefGoogle ScholarPubMed
Crea, A, Guérin, V, Ortega, F & Hartemann, P (1990) Zinc et système immunitaire (Zinc and immune system). Annales de Medecine Interne 141, 447451.Google Scholar
Csermely, P, Szamel, M, Resch, K & Somogyi, J (1988) Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membrane in T lymphocytes. Journal of Biological Chemistry 263, 64876490.Google ScholarPubMed
Cunningham-Rundles, S, Bockman, RS, Lin, A, Giardina, PV, Hilgartner, MW, Caldwell-Brown, D & Carter, DM (1980) Physiological and pharmacological effects of zinc on immune response. Annals of the New York Academy of Sciences 587, 113122.CrossRefGoogle Scholar
De-Rinaldis, E, Pisaneschi, G, Camacho-Vanegas, O & Beccari, E (1998) The binding sites for Xenopus laevis FIII/YY1 in the first exon of L1 and L14 ribosomal protein genes are dispensable for promoter expression. European Journal of Biochemistry 255, 563569.CrossRefGoogle ScholarPubMed
Deuel, TF, Guan, LS & Wang, ZY (1999) Wilms tumor gene product WT1 arrests macrophage differentiation of HL-60 cells through its zinc-finger domain. Biochemical and Biophysical Research Communications 254, 192196.CrossRefGoogle ScholarPubMed
Dowd, PS, Kelleher, J & Guillou, PJ (1986) T-lymphocyte subsets and interleukin-2 production in zinc-deficient rats. British Journal of Nutrition 55, 5969.CrossRefGoogle ScholarPubMed
Driessen, C, Hirv, K, Kirchner, H & Rink, L (1995 a) Divergent effects of zinc on different bacterial pathogenic agents. Journal of Infectious Diseases 171, 486489.CrossRefGoogle ScholarPubMed
Driessen, C, Hirv, K, Kirchner, H & Rink, L (1995 b) Zinc regulates cytokine induction by superantigens and lipopolysaccharide. Immunology 84, 272277.Google ScholarPubMed
Driessen, C, Hirv, K, Rink, L & Kirchner, H (1994) Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. Lymphokine and Cytokine Research 13, 1520.Google ScholarPubMed
Driessen, C, Hirv, K, Wellinghausen, N, Kirchner, H & Rink, L (1995 c) Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide-induced production of IFN-γ and IL-1β by human mononuclear cells. Journal of Leukocyte Biology 57, 904908.CrossRefGoogle Scholar
Duchateau, J, Delespesse, G & Vereecke, P (1981) Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects. American Journal of Clinical Nutrition 34, 8893.CrossRefGoogle ScholarPubMed
Easley, D, Krebs, N, Jefferson, M, Miller, L, Erskine, J, Accurso, F & Hambidge, KM (1998) Effect of pancreatic enzymes on zinc absorption in cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 26, 136139.CrossRefGoogle ScholarPubMed
Esmaeli, B, Burnstine, MA, Martonyi, CL, Sugar, A, Johnson, V & Brewer, GJ (1996) Regression of Kayser-Fleischer rings during oral zinc therapy: correlation with systemic manifestation of WD. Cornea 15, 582588.CrossRefGoogle Scholar
Favier, A & Favier, M (1990) Consequences des deficits en zinc durant la grossesse pour la mère et le nouveau-né (Consequences of zinc deficits during pregnancy for the mother and newborn). Revue Française de Gynecologie et d'Obstetrique 85, 1327.Google Scholar
Favier, AE (1992) The role of zinc in reproduction. Hormonal mechanisms. Biological Trace Element Research 32, 363382.CrossRefGoogle ScholarPubMed
Feduchi, E, Gallego, MI & Lazo, PA (1994) The human zinc-finger protein-7 gene is located 90 kb 3> of MYC and is not expressed in Burkitt lymphoma cell lines. International Journal of Cancer 58, 855859.Google Scholar
Flieger, D, Riethmüller, G & Ziegler-Heitbrock, HWL (1990) Zn2+ inhibits both tumor necrosis factor-mediated DNA fragmentation and cytolysis. International Journal of Cancer 44, 315319.CrossRefGoogle Scholar
Fraker, PJ, Gershwin, ME, Good, RA & Prasad, A (1986) Interrelationships between zinc and immune functions. Federation Proceedings 45, 14741479.Google Scholar
Fraker, PJ, Osati-Ashtiani, F, Wagner, MA & King, LE (1995) Possible roles for glucocorticoids and apoptosis in the suppression of lymphopoiesis during zinc deficiency: a review. Journal of the American College of Nutrition 14, 1117.CrossRefGoogle ScholarPubMed
Fraser, JD, Urban, RG, Strominger, JL & Robinson, H (1992) Zinc regulates the function of two superantigens. Proceedings of the National Academy of Sciences USA 89, 55075511.CrossRefGoogle ScholarPubMed
Fukamachi, Y, Karasaki, Y, Sugiura, T, Itoh, H, Yamamura, K & Higashi, K (1998) Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the Bcl-2/ Bax ratio. Biochemical and Biophysical Research Communications 246, 364369.CrossRefGoogle ScholarPubMed
Gearhart, DA, Neafsey, EJ & Collins, MA (1997) Characterization of brain beta-carboline-2-N-methyltransferase, an enzyme that may play a role in idiopathic Parkinson's disease. Neurochemical Research 22, 113121.CrossRefGoogle ScholarPubMed
German Society of Nutrition (1995) Ausschuß Nahrungsbedarf der DGE Zufuhrempfehlungen und Nährstoffbedarf. Teil II: Vergleich der Vorschläge von SCF/EC mit den Empfehlungen der DGE (Dietary requirements committee of DGE recommended intakes and nutrient requirements. Part 2. Comparison of proposals of SCF/EC with the recommendations of DGE). Ernährungsumschau 42, 410.Google Scholar
Goode, HF, Kelleher, J & Walker, BE (1989) Zinc concentrations in pure populations of peripheral blood neutrophils, lymphocytes and monocytes. Annals of Clinical Biochemistry 26, 8995.CrossRefGoogle ScholarPubMed
Greskas, D, Alivanis, P, Kotzadamis, N, Kiriazopoulos, M & Tourkantonis, A (1992) Influenza vaccination in chronic hemodialysis patients. The effect of zinc supplementation. Renal Failure 14, 575578.CrossRefGoogle Scholar
Groman, N & Judge, K (1979) Effect of metal ions on diphteria toxin production. Infection and Immunity 26, 10651070.Google ScholarPubMed
Hadden, JW (1995) The treatment of zinc is an immunotherapy. International Journal of Immunopharmacology 17, 697701.CrossRefGoogle ScholarPubMed
Heldin, CH (1995) Dimerization of cell surface receptors in signal transduction. Cell 80, 213223.CrossRefGoogle ScholarPubMed
Heng, MK, Song, MK & Heng, MCY (1993) Reciprocity between tissue calmodulin and cAMP levels: modulation by excess zinc. British Journal of Dermatology 129, 280285.CrossRefGoogle ScholarPubMed
Hogstrand, C, Verbost, PM, Bonga, SE & Wood, CM (1996) Mechanisms of zinc uptake in gills of freshwater rainbow trout: interplay with calcium transport. American Journal of Physiology 270, R1141R1147.Google ScholarPubMed
Humeny, A, Bokenkamp, D & Thole, HH (1999) The HDQVH-motif in domain E of the estradiol receptor alpha is responsible for zinc-binding and zinc-induced hormone release. Molecular and Cellular Endocrinology 153, 7178.CrossRefGoogle Scholar
Hynes, M, Stone, DM, Dowd, M, Pitts-Meek, S, Goddard, A, Gurney, A & Rosenthal, A (1997) Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron 19, 1526.CrossRefGoogle ScholarPubMed
Ishido, M, Suzuki, T, Adachi, T & Kunimoto, M (1999) Zinc stimulates DNA synthesis during its antiapoptotic action independently with increments of an antiapoptotic protein, Bcl-2, in porcine kidney LLC-PK cells. Journal of Pharmacology and Experimental Therapeutics 290, 923928.Google Scholar
James, K (1990) Interaction between cytokines and α2-macroglobulin. Immunology Today 11, 163166.CrossRefGoogle Scholar
Jameson, S (1993) Zinc status in pregnancy: the effect of zinc therapy on perinatal mortality, prematurity, and placental ablation. Annals of the New York Academy of Sciences 678, 178192.CrossRefGoogle ScholarPubMed
Jiang, S, Chow, SC, McCabe, MJ Jr & Orrenius, S (1995) Lack of Ca2+ involvement in thymocyte apoptosis induced by chelation of intracellular Zn2+. Laboratory Investigation 73, 111117.Google ScholarPubMed
Kawahara, M, Arispe, N, Kuroda, Y, Rojas, E (1997) Alzheimer's disease amyloid beta-protein forms Zn(2+)-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons. Biophysical Journal 73, 6775.CrossRefGoogle ScholarPubMed
Keen, CL & Gershwin, ME (1990) Zinc deficiency and immune function. Annual Review of Nutrition 10, 415431.CrossRefGoogle ScholarPubMed
Kim, J, Urban, RG, Strominger, JL & Wiley, DC (1994) Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. Science 266, 18701878.CrossRefGoogle ScholarPubMed
Kirchner, H & Rühl, H (1970) Stimulation of human peripheral lymphocytes by Zn2+ in vitro. Experimental Cell Research 61, 229230.CrossRefGoogle ScholarPubMed
Klaiman, AP, Victery, W, Kluger, MJ & Vander, AJ (1981) Urinary excretion of zinc and iron following acute injection of dead bacteria in dog. Proceedings of the Society for Experimental Biology and Medicine 167, 165171.CrossRefGoogle Scholar
Klosterhalfen, B, Töns, C, Hauptmann, S, Tietze, L, Offner, FA, Küpper, W & Kirkpatrick, CJ (1996) Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. Biochemical Pharmacology 52, 12011210.CrossRefGoogle Scholar
Krasovec, M & Frenk, E (1996) Acrodermatitis enteropathica secondary to Crohn's disease. Dermatology 193, 361363.CrossRefGoogle ScholarPubMed
Kreft, B, Fischer, A, Krüger, S, Sack, K, Kirchner, H & Rink, L (2000) The impaired immune response to diphtheria vaccination in elderly chronic hemodialysis patients is related to zinc deficiency. Biogerontology 1, 6166.CrossRefGoogle ScholarPubMed
Kruse-Jarres, JD (1989) The significance of zinc for humoral and cellular immunity. Journal of Trace Elements and Electrolytes in Health and Diseases 3, 18.Google ScholarPubMed
Lighart, GJ, Coberand, JX, Fournier, C, Galanaud, P, Hijmans, W, Kennes, B, Müller-Hermelink, HK & Steinmann, GG (1984) Admission criteria for immunogerontological studies in man: The Senieur Protocol. Mechanisms of Ageing and Development 28, 4755.CrossRefGoogle Scholar
Lin, H, Zhu, YJ & Lal, R (1999) Amyloid beta protein (1–40) forms calcium permeable, Zn2+-sensitive channel in reconstituted lipid vesicles. Biochemistry 38, 1118911196.CrossRefGoogle ScholarPubMed
Maret, W (1998) The glutathione redox state and zinc mobilization from metallothionein and other proteins with zinc-sulfur coordination sites. In Glutathione in the Nervous System, pp. 257273 [Shaw, CA, editor]. Philadelphia, PA: Taylor & Francis.Google Scholar
Maret, W, Jacob, C, Vallee, BL & Fischer, EH (1999) Inhibitory sites in enzymes: Zinc removal and reactivation by thionein. Proceedings of the National Academy of Sciences USA 96, 19361940.CrossRefGoogle ScholarPubMed
Mills, CF (1989) Zinc in Human Biology. Human Nutrition Reviews. London: Springer Verlag.CrossRefGoogle Scholar
Mocchegiani, E, Santarelli, L, Muzzioli, M & Fabris, N (1995 a) Reversibility of the thymic involution and of age-related peripheral immune dysfunction by zinc supplementation in old mice. International Journal of Immunopharmacology 17, 703718.CrossRefGoogle Scholar
Mocchegiani, E, Veccia, S, Ancarani, F, Scalise, G & Fabris, N (1995 b) Benefit of oral zinc supplementation as an adjunct to zidovudine (AZT) therapy against opportunistic infections in AIDS. International Journal of Immunopharmacology 17, 719727.CrossRefGoogle ScholarPubMed
Mossad, SB, Macknin, ML, Medendorp, SV & Mason, P (1996) Zinc gluconate lozenges for treating the common cold. Annals of Internal Medicine 125, 8188.CrossRefGoogle ScholarPubMed
Muraosa, Y, Takahashi, K, Yoshizawa, M & Shibahara, S (1996) cDNA cloning of a novel protein containing two zinc-finger domains that may function as a transcription factor for the human heme-oxygenase-1 gene. European Journal of Biochemistry 23, 471479.CrossRefGoogle Scholar
Murthy, ARK, Lehrer, RI, Harwig, SSL & Miyasaki, KT (1993) In vitro candidastatic properties of the human neutrophil calprotectin complex. Journal of Immunology 151, 62916301.Google ScholarPubMed
Myung, SJ, Yang, SK, Jung, HY, Jung, SA, Kang, GH, Ha, HK, Hong, WS & Min, Y (1998) Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease. Journal of Gastroenterology 33, 876879.CrossRefGoogle Scholar
Najim, RA, Sharquie, KE & Farjou, IB (1998) Zinc sulphate in the treatment of cutaneous leishmaniasis: an in vitro and animal study. Memorias do Instituto Oswaldo Cruz 93, 831837.CrossRefGoogle Scholar
Nakayama, H, Scott, IC & Cross, JC (1998) The transition to endoreduplication in trophoblast giant cells is regulated by the mSNA zinc finger transcription factor. Developmental Biology 199, 150163.CrossRefGoogle ScholarPubMed
Neldner, KH & Hambidge, KM (1975) Zinc therapy in acrodermatitis enteropathica. New England Journal of Medicine 292, 879882.CrossRefGoogle ScholarPubMed
Neves, I Jr, Bertho, AL, Veloso, VG, Nascimento, DV, Campos-Mello, DL & Morgado, MG (1998) Improvement of the lymphoproliferative immune response and apoptosis inhibition upon in vitro treatment with zinc of peripheral blood mononuclear cells (PBMC) from HIV+ individuals. Clinical and Experimental Immunology 111, 264268.CrossRefGoogle ScholarPubMed
Nowak, G (1998) Alterations in zinc homeostasis in depression and antidepressant therapy. Polish Journal of Pharmacology 50, 14.Google ScholarPubMed
Nowak, G & Schlegel-Zawadzka, M (1999) Alterations in serum and brain trace element levels after antidepressant treatment: part I. Zinc. Biological Trace Element Research 67, 8592.CrossRefGoogle ScholarPubMed
O'Halloran, TV (1993) Transition metals in control of gene expression. Science 261, 715725.CrossRefGoogle ScholarPubMed
Osati-Ashtiani, F, King, LE & Fraker, PJ (1998) Variance in the resistance of murine early bone marrow B cells to a deficiency in zinc. Immunology 94, 94100.CrossRefGoogle ScholarPubMed
Palmiter, RD & Findley, SD (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO Journal 14, 639649.Google Scholar
Palmiter, RD, Cole, TB & Findley, SD (1996 a) ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO Journal 15, 17841791.Google ScholarPubMed
Palmiter, RD, Cole, TB, Quaife, CJ & Findley, SD (1996 b) ZnT-3, a putative transporter of zinc into synaptic vesicles. Proceedings of the National Academy of Sciences USA 93, 1493414939.CrossRefGoogle ScholarPubMed
Patterson, WP, Winkelmann, M & Perry, MC (1985) Zinc-induced copper deficiency: megamineral sideroblastic anemia. Annals of Internal Medicine 103, 385386.CrossRefGoogle ScholarPubMed
Pavletich, NP & Pabo, CO (1993) Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science 261, 17011707.CrossRefGoogle ScholarPubMed
Philipsen, S & Suske, G (1999) A tale of three fingers: the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Research 27, 29913000.CrossRefGoogle ScholarPubMed
Phillips, JL & Azari, P (1974) Zinc transferrin: Enhancement of nucleic acid synthesis in phytohemagglutinin-stimulated human lymphocytes. Cellular Immunology 10, 3137.CrossRefGoogle ScholarPubMed
Pohl, E, Qui, X, Must, LM, Holmes, RK & Hol, WG (1997) Comparison of high-resolution structures of the diphteria toxin repressor in complex with cobalt and zinc at the cation-anion binding site. Protein Science 6, 11141118.CrossRefGoogle ScholarPubMed
Porter, KG, McMaster, D, Elmes, ME & Love, AH (1977) Anaemia and low serum-copper during zinc therapy. Lancet ii, 774.CrossRefGoogle Scholar
Prasad, AS (1995) Zinc: an overview. Nutrition 11, 9399.Google ScholarPubMed
Prasad, AS (1996) Zinc deficiency in women, infants and children. Journal of the American College of Nutrition 15, 113120.CrossRefGoogle Scholar
Prasad, AS, Beck, FW, Kaplan, J, Chandrasekar, PH, Ortega, J, Fitzgerald, JT & Swerdlow, P (1999) Effect of zinc supplementation on incidence of infections and hospital admission in sickle cell disease (SCD). American Journal of Hematology 61, 194202.3.0.CO;2-C>CrossRefGoogle Scholar
Prasad, AS, Miaie, A Jr, Farid, Z, Schulert, A & Sandstead, HH (1963) Zinc metabolism in patients with the syndrome of iron deficiency, hypogonadism and dwarfism. Journal of Laboratory and Clinical Medicine 83, 537549.Google Scholar
Provinciali, M, Montenovo, A, Di-Stefano, G, Colombo, M, Daghetta, L, Cairati, M, Veroni, C, Cassino, R, Della-Torre, F & Fabris, N (1998) Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. Age and Ageing 27, 715722.CrossRefGoogle ScholarPubMed
Rajagopalan, S, Winter, CC, Wagtmann, N & Long, EO (1995) The Ig-related killer cell inhibitory receptor binds zinc and requires zinc for recognition of HLA-C on target cells. Journal of Immunology 155, 41434146.Google ScholarPubMed
Raulin, J (1869) Etudes chimique sur la vegetation (Chemical studies on plants). Annales des Sciences Naturelles Botanique et Biologie Vegetale 11, 293299.Google Scholar
Rawer, P, Willems, WR, Breidenbach, T, Guttmann, W, Pabst, W & Schutterle, G (1987) Seroconversion rate hepatitis B vaccination, hemodialysis, and zinc supplementation. Kidney International 22S, 149152.Google Scholar
Reinhold, D, Ansorge, S & Grüngreiff, K (1999) Immunobiology of zinc and zinc therapy. Immunology Today 20, 102.CrossRefGoogle ScholarPubMed
Rink, L & Kirchner, H (1999) Reply to Reinhold et al. Immunology Today 20, 102103.CrossRefGoogle Scholar
Rühl, H & Kirchner, H (1978) Monocyte-dependent stimulation of human T cells by zinc. Clinical and Experimental Immunology 32, 484488.Google Scholar
Rühl, H, Kirchner, H & Borchert, G (1971) Kinetics of the Zn2+-stimulation of human peripheral lymphocytes in vitro. Proceedings of the Society for Experimental Biology and Medicine 137, 10891092.CrossRefGoogle Scholar
Safie-Garabedian, B, Ahmed, K, Khamashta, MA, Taub, NA & Hughes, GRV (1993) Thymulin modulates cytokine release by peripheral blood mononuclear cells: a comparison between healthy volunteers and patients with systemic lupus erythematodes. International Archives of Allergy and Immunology 101, 126131.CrossRefGoogle Scholar
Saha, AR, Hadden, EM & Hadden, JW (1995) Zinc induces thymulin secretion from human thymic epithelial cells in vitro and augments splenocyte and thymocyte responses in vivo. International Journal of Immunopharmacology 17, 729733.CrossRefGoogle ScholarPubMed
Sakai, Y, Nakagawa, R, Sato, R & Maeda, M (1998) Selection of DNA binding sites for human transcriptional regulator GATA-6. Biochemical and Biophysical Research Communications 250, 682688.CrossRefGoogle ScholarPubMed
Salas, M & Kirchner, H (1987) Induction of interferon-γ in human leukocyte cultures stimulated by Zn2+. Clinical Immunology and Immunopathology 45, 139142.CrossRefGoogle ScholarPubMed
Sampson, B, Kovar, IZ, Rauscher, A, Fairweather-Tait, S, Beattie, J, McArdle, HJ, Ahmed, R & Green, C (1997) A case of hyperzincemia with functional zinc depletion: a new disorder? Pediatric Research 42, 219225.CrossRefGoogle ScholarPubMed
Sandstead, HH, Henriksen, LK, Greger, JL, Prasad, AS & Good, RA (1982) Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing. American Journal of Clinical Nutrition 36, 10461059.CrossRefGoogle ScholarPubMed
Schoenmakers, E, Alen, P, Verrijdt, G, Peeters, B, Verhoeven, G, Rombauts, W & Claessens, F (1999) Differential DNA binding by the androgen and glucocorticoid receptors involves the second Zn-finger and a C-terminal extension of the DNA-binding domains. Biochemical Journal 341, 515521.CrossRefGoogle Scholar
Scholl, TO, Hediger, ML, Schall, JI, Fischer, RL & Khoo, CS (1993) Low zinc intake during pregnancy: its association with preterm and very preterm delivery. American Journal of Epidemiology 137, 11151124.CrossRefGoogle ScholarPubMed
Scott, BJ & Bradwell, AR (1983) Identification of the serum binding proteins for iron, zinc, cadmium, nickel and calcium. Clinical Chemistry 29, 629633.Google ScholarPubMed
Scuderi, P (1990) Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. Cellular Immunology 126, 391405.CrossRefGoogle ScholarPubMed
Shimizu, N, Yamauchi, Y & Aoki, T (1999) Treatment and management of Wilson's disease. Pediatrics International 41, 419422.CrossRefGoogle ScholarPubMed
Simkin, PA (1976) Oral zinc sulphate in rheumatoid arthritis. Lancet ii, 539542.CrossRefGoogle Scholar
Skamoto, A, Omirulleh, S, Nakayama, T & Iwabuchi, M (1996) A zinc-finger-type transcription factor WZF-1 that binds to a novel cis-acting element of histone gene promoters represses its own promoter. Plant and Cellular Physiology 37, 557562.CrossRefGoogle Scholar
Sohnle, PG, Collins-Lech, C & Wiessner, JH (1991) The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants. Journal of Infectious Diseases 164, 137142.CrossRefGoogle ScholarPubMed
Song, A, Chen, YF, Thamatrakoln, K, Storm, TA & Krensky, AM (1999) RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. Immunity 10, 93103.CrossRefGoogle ScholarPubMed
Sood, SM, Wu, MX, Hill, KA & Slattery, CW (1999) Characterization of zinc-depleted alanyl-tRNA synthetase from Escherichia coli: role of zinc. Archives of Biochemistry and Biophysics 368, 380384.CrossRefGoogle ScholarPubMed
Sturniolo, GC, Mestriner, C, Irato, P, Albergoni, V, Longo, G & D'Inca, R (1999) Zinc therapy increases duodenal concentrations of metallothionein and iron in Wilson's disease patients. American Journal of Gastroenterology 94, 334338.CrossRefGoogle ScholarPubMed
Sundström, M, Abrahamsen, L, Antonsson, P, Mehindate, K, Mourad, W & Dohlsten, M (1996) The crystal structure of staphylococcal enterotoxin type D reveals Zn2+ mediated homodimerization. EMBO Journal 15, 68326840.Google ScholarPubMed
Tanaka, Y, Shiozawa, S, Morimoto, I & Fujita, T (1989) Zinc inhibits pokeweed mitogen-induced development of immunoglobulin-secreting cells through augmentation of both CD4 and CD8 cells. International Journal of Immunopharmacology 11, 673679.CrossRefGoogle ScholarPubMed
Taylor, GA & Blackshear, PJ (1995) Zinc inhibits turnover of labile mRNAs in intact cells. Journal of Cellular Physiology 162, 378387.CrossRefGoogle ScholarPubMed
The Finnish-German APECED Consortium (1997) An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. Nature Genetics 17, 399403.CrossRefGoogle Scholar
Tierno, PM Jr & Hanna, BA (1985) In vitro amplification of toxic shock syndrome toxin-1 by intravaginal devices. Contraception 31, 185194.CrossRefGoogle ScholarPubMed
Todd, WK, Elvelym, A & Hart, EB (1934) Zinc in the nutrition of the rat. American Journal of Physiology 107, 146156.Google Scholar
Trubiani, O, Antonucci, A, Palka, G & Di-Primio, R (1996) Programmed cell death of peripheral myeloid precursor cells in Down patients: effect of zinc therapy. Ultrastructural Pathology 20, 457462.CrossRefGoogle ScholarPubMed
Tsuda, M, Imaizumi, K, Katayama, T, Kitagawa, K, Wanaka, A, Tohyama, M & Takagi, T (1997) Expression of zinc transporter gene, ZnT-1, is induced after transient forebrain ischemia in the gerbil. Journal of Neuroscience 17, 66786684.Google ScholarPubMed
Turk, S, Bozfakioglu, S, Ecder, ST, Kahraman, T, Gurel, N, Erkoc, , Aysuna, N, Turkmen, A, Bekiroglu, N & Ark, E (1998) Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients. International Journal of Artificial Organs 21, 274278.CrossRefGoogle ScholarPubMed
Turner, J & Crossley, M (1998) Cloning and characterization of mCtBP2, a co-repressor that associates with basic Kruppel-like factor and other mammalian transcriptional regulators. EMBO Journal 17, 51295140.CrossRefGoogle ScholarPubMed
Umezawa, K, Nakazawa, K, Uchihata, Y & Otsuka, M (1999) Screening for inducers of apoptosis in apoptosis-resistant human carcinoma cells. Advances in Enzyme Regulation 39, 145156.CrossRefGoogle ScholarPubMed
Valberg, LS, Flanagan, PR & Chamberlain, MJ (1984) Effect of iron, tin and copper on zinc absorption in humans. American Journal of Clinical Nutrition 40, 536541.CrossRefGoogle ScholarPubMed
Vallee, BL & Falchuk, KH (1993) The biochemical basis of zinc physiology. Physiological Reviews 73, 79118.CrossRefGoogle ScholarPubMed
Varadinova, TL, Bontchev, PR, Nachev, CK, Shishkov, SA, Strachilov, D, Paskalev, Z, Toutekova, A & Panteva, M (1993) Mode of action of Zn-complexes on herpes simplex virus type 1 infection in vitro. Journal of Chemotherapy 5, 39.CrossRefGoogle ScholarPubMed
Villiers, MB, Gabert, FM, Jacquier, MR & Colomb, MG (1993) Involvement of the Zn-binding region of the tetanus toxin in B and T recognition. Influence of Zn fixation. Molecular Immunology 30, 129136.CrossRefGoogle Scholar
Warner, GL & Lawrence, DA (1986) Stimulation of murine lymphocyte response by cations. Cellullar Immunology 101, 425439.CrossRefGoogle ScholarPubMed
Weiss, G, Wachter, H & Fuchs, D (1995) Linkage of cell-mediated immunity to iron metabolism. Immunology Today 16, 495500.CrossRefGoogle ScholarPubMed
Weiss, G, Widner, B, Zoller, H & Fuchs, D (1998) The immunobiology of zinc and the kidney. Immunology Today 19, 193.CrossRefGoogle ScholarPubMed
Wellinghausen, N, Driessen, C & Rink, L (1996 a) Stimulation of human peripheral blood mononuclear cells by zinc and related cations. Cytokine 18, 767771.CrossRefGoogle Scholar
Wellinghausen, N, Fischer, A, Kirchner, H & Rink, L (1996 b) Interaction of zinc ions with human peripheral blood mononuclear cells. Cellular Immunology 171, 255261.CrossRefGoogle ScholarPubMed
Wellinghausen, N, Kern, WV, Jöchle, W & Kern, P (2000) Zinc serum level in human deficiency virus infected patients in relation to immunological status. Biological Trace Element Research 73, 7989.CrossRefGoogle ScholarPubMed
Wellinghausen, N, Kirchner, H & Rink, L (1997 a) The immunobiology of zinc. Immunology Today 18, 519521.CrossRefGoogle ScholarPubMed
Wellinghausen, N, Martin, M & Rink, L (1997 b) Zinc inhibits IL-1 dependent T cell stimulation. European Journal of Immunology 27, 25292535.CrossRefGoogle ScholarPubMed
Wellinghausen, N, Schromm, AB, Seydel, U, Brandenburg, K, Luhm, J, Kirchner, H & Rink, L (1996 c) Zinc enhances lipopolysaccharide-induced monokine secretion by a fluidity change of lipopolysaccharide. Journal of Immunology 157, 31393145.Google Scholar
Williams, AJ, Khachigian, LM, Shows, T & Collins, T (1995) Isolation and characterization of a novel zinc-finger protein with transcription repressor activity. Journal of Biological Chemistry 270, 2214322152.CrossRefGoogle ScholarPubMed
Worwag, M, Classen, HG & Schumacher, E (1999) Prevalence of magnesium and zinc in nursing home residents in Germany. Magnesium Research 12, 181189.Google ScholarPubMed
Wright, SD & Kolesnick, RN (1995) Does endotoxin stimulate cells by mimicking ceramide? Immunology Today 16, 297302.CrossRefGoogle ScholarPubMed
Yamagata, K, Kaufmann, WE, Lanahan, A, Papapavlou, M, Barnes, CA, Andreasson, KI & Worley, PF (1994) Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268. Learning and Memory 1, 140152.Google ScholarPubMed
Yang, XW, Zhong, R & Heintz, N (1996) Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49. Development 122, 555566.Google ScholarPubMed
Yuzbasiyan-Gurkan, VA, Brewer, GJ, Vander, AJ, Guenter, MJ & Prasad, AS (1989) Net renal tubular reabsorption of zinc in healthy man and impaired handling in sickle cell anemia. American Journal of Hematology 31, 8790.CrossRefGoogle ScholarPubMed
Zalewski, PD & Forbes, IJ (1993) Intracellular zinc and the regulation of apoptosis. In Programmed Cell Death: The Cellular and Molecular Biology of Apoptosis, pp. 7385[Laviri, M and Watters, D, editors\. Melbourne: Harword Academic Press.Google Scholar
Ziegler, EE, Serfass, RE, Nelson, SE, Figueroa-Colon, R, Edwards, BB, Houk, RS & Thompson, JJ (1989) Effect of low zinc intake on absorption and excretion of zinc by infants studied with 70Zn as extrinsic tag. Journal of Nutrition 119, 16471653.CrossRefGoogle ScholarPubMed
Zoli, A, Altomonte, L, Caricchio, R, Gaossi, A, Mirone, L, Ruffini, MP & Magaro, M (1998) Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1 beta and tumour necrosis factor alpha. Clinical Rheumatology 17, 378382.CrossRefGoogle ScholarPubMed