Skip to main content
SpringerLink
Log in

Effects of Copper Deficiency on the Immune System

  • Chapter
Antioxidant Nutrients and Immune Functions

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 262))

Abstract

Copper is an essential metal for proper functioning of all living systems. Biochemical mechanisms have evolved that result in homeostatic balance of copper. This ensures that adequate but not toxic levels are absorbed, transported, utilized, and excreted. Throughout the biological kingdom copper expresses its function through specific ligands as free copper ion is rapidly complexed. These ligands are usually specific cuproenzymes. Knowledge of these cuproenzymes forms the basis of our current understanding of the biochemical function of copper (Prohaska, 1988).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Allen, K. G. D., and Klevay, L. M., 1978, Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency, Atherosclerosis, 29:81–93.

    Article  CAS  Google Scholar 

  • Allen, K. G. D., Arthur, J. R., Morrice, P. C., Nicol, F., and Mills, C. F., 1988, Copper deficiency and tissue glutathione concentration in the rat (42634), Proc. Soc. Exp. Biol. Med., 187:38–43.

    CAS  Google Scholar 

  • Barnea, A., Cho., G., and Hartter, D. E., 1988, A correlation between the ligand specificity for 67copper uptake and for copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from median eminence explants, Endocrinology, 122:1505–1510.

    Article  CAS  Google Scholar 

  • Bell, J. G., Keen, C. L., and Lönnerdal, B., 1987, Effect of infant cereals on zinc and copper absorption during weaning, Am. J. Dis. Child., 141:1128–1132.

    CAS  Google Scholar 

  • Besedovsky, H., Del Rey, A., Sorkin, E., Da Prada, M., Burri, R., and Honegger, C., 1983, The immune response evokes changes in brain noradrenergic neurons, Science, 221:564–566.

    Article  CAS  Google Scholar 

  • Blakley, B. R., and Hamilton, D. L., 1987, The effect of copper deficiency on the immune response in mice, Drug-Nutr. Interactions, 5:103–111.

    CAS  Google Scholar 

  • Boyne, R., and Arthur, J. R., 1981, Effects of selenium and copper deficiency on neutrophil function in cattle, J. Comp. Pathol., 91:271–276.

    Article  CAS  Google Scholar 

  • Boyne, R., and Arthur, J. R., 1986, Effects of molybdenum or iron induced copper deficiency on the viability and function of neutrophils from cattle, Res. Vet. Sci., 41:417–419.

    CAS  Google Scholar 

  • Castillo-Duran, C., Fisberg, M., Valenzuela, A., Egaana, J. I., and Uauy, R., 1983, Controlled trial of copper supplementation during the recovery from marasmus, Am. J. Clin. Nutr., 37: 898–903.

    CAS  Google Scholar 

  • Danks, D. M., Campbell, P. E., Stevens, B. J., Mayne, V., and Cartwright, E., 1972, Menkes’s kinky hair syndrome, Pediatrics, 50:188–201.

    CAS  Google Scholar 

  • Davis, M. A., Johnson, W. T., Briske-Anderson, M., and Kramer, T. R., 1987, Lymphoid cell functions during copper deficiency, Nutr. Res., 7:211–222.

    Article  CAS  Google Scholar 

  • DePasquale-Jardieu, P., and Fraker, P. J., 1980, 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., 124:2650–2655.

    CAS  Google Scholar 

  • Duwe, A. K., Fitch, M., and Ostwald, R., 1981, Effects of dietary cholesterol on antibody- dependent phagocytosis and cell-mediated lysis in guinea pigs, J. Nutr., Ill: 1672–1680.

    Google Scholar 

  • Eason, S., Carville, D., Strain, J. J., and Hannigan, B. M., 1988, The influence of dietary carbohydrate on antibody-mediated immunity in copper deficiency, Biochem. Soc. Trans., 16:54–55.

    CAS  Google Scholar 

  • Eipper B. A., Mains, R. E., and Glembotski, C. C., 1983, Identification in pituitary tissue of a peptide α-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid, Proc. Natl. Acad. Sci. USA, 80:5144–5148.

    Article  CAS  Google Scholar 

  • Erickson, R. R., Prasad, J. S., and Holtzman, J. L., 1987, The role of NADPH- and reduced glutathione-dependent enzymes in the norepinephrine modulation of the ATP-dependent, hepatic microsomal calcium pump: a new pathway for the noradrenergic regulation of cytosolic calcium in the hepatocyte, J. Pharmacol. Exp. Ther., 242:472–477.

    CAS  Google Scholar 

  • Failla, M. L., Babu, U., and Seidel, K. E, 1988, Use of immunoresponsiveness to demonstrate that the dietary requirement for copper in young rats is greater with dietary fructose than dietary starch, J. Nutr., 118:487–496.

    CAS  Google Scholar 

  • Farquharson, C, and Robins, S. P., 1988, Female rats are susceptible to cardiac hypertrophy induced by copper deficiency: the lack of influence of estrogen and testosterone, Proc. Soc. Exp. Biol. Med., 188:272–281.

    CAS  Google Scholar 

  • Flynn, A., Loftus, M. A., and Finke, J. H., 1984, Production of interleukin-1 and interleukin- 2 in allogeneic mixed lymphocyte cultures under copper, magnesium and zinc deficient conditions, Nutr. Res., 4:673–679.

    Article  CAS  Google Scholar 

  • Flynn, A., and Yen, B. R., 1981, Mineral deficiency effects on the generation of cytotoxic T- cells and T-helper cell factors in vitro, J. Nutr., 111:907–913.

    CAS  Google Scholar 

  • Gibson, R. S., 1985, Dietary intakes of trace elements in young children, Food Nutr. News, 57: 21–24.

    Google Scholar 

  • Gross, A.M., and Prohaska, J.R., 1989, Copper-deficient mice have higher cardiac norepinephrine turnover, Fed. Proc. 48:in press.

    Google Scholar 

  • Grossman, C. J., 1985, Interactions between the gonadal steroids and the immune sytstem, Science, 227:257–261.

    Article  CAS  Google Scholar 

  • Habig, W. H., Pabst, M. J., and Jakoby, W. B., 1974, Glutathione S-transferases. The first enzymatic step in mercapturic acid formation, J. Biol. Chem., 249:7130–7139.

    CAS  Google Scholar 

  • Haschke, F., Ziegler, E. E., Edwards, B. B., and Fomon, S. J., 1986, Effect of iron fortification of infant formula on trace mineral absorption, J. Ped. Gastroenterol. Nutr., 5:768–773.

    Article  CAS  Google Scholar 

  • Heresi, G., Castillo-Durán, C., Muñoz, C., Arévalo, M., and Schlesinger, L., 1985, Phagocytosis and immunoglobulin levels in hypocupremic infants, Nutr. Res., 5:1327–1334.

    Article  Google Scholar 

  • Hoffmann, M. K., Mizel, S. B., and Hirst, J. A., 1984, IL 1 requirement for B cell activation revealed by use of adult serum, J. Immunol., 133:2566–2568.

    CAS  Google Scholar 

  • Jain, S. K., and Williams, D. M., 1988, Copper deficiency anemia: altered red blood cell lipids and viscosity in rats, Am. J. Clin. Nutr., 48:637–640.

    CAS  Google Scholar 

  • James, S. J., Swendseid, M., and Makinodan, T., 1987, Macrophage-mediated depression of T-cell proliferation in zinc-deficient mice, J. Nutr., 117:1982–1988.

    CAS  Google Scholar 

  • Johnson, W. T., and Kramer, T. R., 1987, Effect of copper deficiency on erythrocyte membrane proteins in rats, J. Nutr., 117:1085–1090.

    CAS  Google Scholar 

  • Jones, D. G., 1984, Effects of dietary copper depletion on acute and delayed inflammatory responses in mice, Res. Vet. Sci., 37:205–210.

    CAS  Google Scholar 

  • Jones, D. G., and Suttle, N. F., 1981, Some effects of copper deficiency on leucocyte function in sheep and cattle, Res. Yet. Science, 31:151–156.

    CAS  Google Scholar 

  • Jones, D. G., and Suttle, N. F., 1983, The effect of copper dieficiency on the resistance of mice to infection with Pasteurella haemolytica, J. Comp. Pathol., 93:143–149.

    Article  CAS  Google Scholar 

  • Kishore, V., Latman, N., Roberts, D. W., Barnett, J. B., and Sorenson, J. R. J., 1984, Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat, Agents and Actions, 14:274–282.

    Article  CAS  Google Scholar 

  • Koller, L. D., Mulhern, S. A., Frankel, N. C., Steven, M. G., and Williams, J. R., 1987, Immune dysfunction in rats fed a diet deficient in copper, Am. J. Clin. Nutr., 45:997–1006.

    CAS  Google Scholar 

  • Korte, J.J., Bailey, W.R., and Prohaska, J.R., 1988, Copper deficiency impairs development of murine hepatic glutathione transferase MII, Fed. Proc., 47: A1105.

    Google Scholar 

  • Korte, J. J., and Prohaska, J. R., 1987, Dietary copper deficiency alters protein and lipid composition of murine lymphocyte plasma membranes, J. Nutjr., 117:1076–1084.

    CAS  Google Scholar 

  • Kramer, T. R., Johnson, W. T., and Briske-Anderson, M., 1988, Influence of iron and the sex of rats on hematological, biochemical and immunological changes during copper deficiency, J. Nutr, 118:214–221.

    CAS  Google Scholar 

  • Lampi, K. J., Mathias, M. M., Rengers, B. D., and Allen, K. G. D., 1988, Dietary copper and copper dependent superoxide dismutase in hepatic prostaglandin synthesis by rat liver homogenates, Nutr. Res., 8:1191–1202.

    Article  CAS  Google Scholar 

  • Lawrence, R. A., and Jenkinson, S. G., 1987, Effects of copper deficiency on carbon tetrachloride-induĉed lipid peroxidation, J. Lab. Clin. Med 109:134–140.

    CAS  Google Scholar 

  • Lei, K. Y., Rosenstein, F., Shi, F., Hassel, C. A., Carr, T. P., and Zhang, J., 1988, Alterations in lipid composition and fluidity of liver plasma membranes in copper-deficient rats, Proc. Soc. Exp. Biol. Med., 188:335–341.

    CAS  Google Scholar 

  • Lukasewycz, O. A., Kolquist, K. L., and Prohaska, J. R., 1987, Splenocytes from copper- deficient mice are low responders and weak stimulators in mixed lymphocyte reactions, Nutr. Res., 7:43–52.

    Article  CAS  Google Scholar 

  • Lukasewycz, O. A., Kolquist, K. L., and Prohaska, J. R., 1988, Modulation in immunoglobulin (Ig) isotype production in copper-deficient mice, FASEB J., 2:A436.

    Google Scholar 

  • Lukasewycz, O. A., and Prohaska, J. R., 1982, Immunization against transplantable leukemia impaired in copper deficient mice, J. Natl. Cancer Inst., 69:489–493.

    CAS  Google Scholar 

  • Lukasewycz, O. A., and Prohaska, J. R., 1983, Lymphocytes from copper-deficient mice exhibit decreased mitogen reactivity, Nutr. Res., 3:335–341.

    Article  CAS  Google Scholar 

  • Lukasewycz, O. A., and Prohaska, J. R., 1989, Increased interleukin-1 (IL-1) and decreased interleukin-2 (IL-2) production in copper-deficient mice, FASEB J., 3:A665.

    Google Scholar 

  • Lukasewycz, O. A., Prohaska, J. R., Meyer, S. G., Schmidtke, J. R., Hatfield, S. M., and Marder, P., 1985, Alterations in lymphocyte subpopulations in copper-deficient mice, Infect. Immun., 48:644–647.

    CAS  Google Scholar 

  • Markwell, M. A. K., Haas, S. M., Bieber, L. L., and Tolbert, N. E., 1978, Modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples, Anal. Biochem., 87: 206–210.

    Article  CAS  Google Scholar 

  • Mishell, R. I., and Dutton R. W., 1967, Immunization of dissociated spleen cell cultures from normal mice, J. Exp. Med., 126:423–442.

    Article  CAS  Google Scholar 

  • Mitchell, L. L., Allen, K. G. D., and Mathias, M. M., 1988, Copper deficiency depresses rat aortae superoxide dismutase activity and prostacyclin synthesis, Prostaglandins, 35:977–986.

    Article  CAS  Google Scholar 

  • Miyajima, A., Miyatake, S., Schreurs, J., De Vries, J., Arai, N., Yokota, T., and Arai, E.-I., 1988, Coordinate regulation of immune and inflammatory responses by T cell-derived lymphokines, FASEB J., 2:2462–2473.

    CAS  Google Scholar 

  • Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., and Coffman, R. L., 1986, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol., 136:2348–2357.

    CAS  Google Scholar 

  • Mulhern, S. A., and Koller, L. D., 1988, Severe or marginal copper deficiency results in a graded reduction in immune status in mice, J. Nutr., 118:1041–1047.

    CAS  Google Scholar 

  • Mulhern, S. A., Raveche, E. S., Smith, H. R., and Lal, R. B., 1987, Dietary copper deficiency and autoimmunity in the NZB mouse, Am. J. Clin. Nutr., 46:1035–1039.

    CAS  Google Scholar 

  • Newberne, P. M., Hunt, C. E., and Young, V. R., 1968, The role of diet and the reticuloendothelial system in the response of rats to Samonella typhimurium infection, Br. J. Exp. Pathol., 49:448–457.

    CAS  Google Scholar 

  • Noelle, R. J., and Lawrence, D. A., 1981, Determination of glutathione in lymphocytes and possible association of redox state and proliferative capacity of lymphocytes, Biochem. J., 198:571–579.

    CAS  Google Scholar 

  • O’Dorisio, M. S., Wood, C. L., and O’Dorisio, T. M., 1985, Vasoactive intestinal peptide and neuropeptide modulation of the immune response, J. Immunol., 135:792s-796s.

    Google Scholar 

  • Oppenheimer, S. M., Hoffbrand, B. I., Dormandy, T. L., Parker, N., and Wickens, D. G., 1987, Macrocytic anaemia due to copper deficiency in a patient with late onset hypogammaglobulinaemia, Postgrad. Med. J., 63:205–207.

    Article  CAS  Google Scholar 

  • Pletcher, J. M., and Banting, L. F., 1983, Copper deficiency in piglets characterized by spongy myelopathy and degenerative lesions in the great blood vessels, J. So.Af. Vet Assoc., 54:43–46.

    CAS  Google Scholar 

  • Prohaska, J. R., 1983, Changes in tissue growth, concentrations of copper, iron, cytochrome oxidase and superoxide dismutase subsequent to dietary or genetic copper deficiency in mice, J. Nutr., 113:2048–2058.

    CAS  Google Scholar 

  • Prohaska, J. R., 1988, Biochemical functions of copper in animals, in: “Essential and Toxic Elements in Human Health and Disease,” A. S. Prasad, ed., Alan R. Liss, Inc., New York, NY, pp.105–124.

    Google Scholar 

  • Prohaska, J. R., and Cox, D. A., 1983, Decreased brain ascorbate levels in copper-deficient mice and in brindled mice, J. Nutr., 113:2623–2629.

    CAS  Google Scholar 

  • Prohaska, J. R., Cox, D. A., and Bailey, W. R., 1984, Ascorbic acid synthesis and concentrations in organs of copper-deficient and brindled mice, Biol. Trace Elem. Res., 6:441–453.

    Article  CAS  Google Scholar 

  • Prohaska, J. R., and DeLuca, K. L., 1988, Norepinephrine and dopamine distribution in copper-deficient mice, in: “Trace Elements in Man and Animals 6,” L. S. Hurley, C. L. Keen, B. Lonnerdal, and R. B. Rucker, eds., Plenum Press, New York, NY, pp. 109–111.

    Google Scholar 

  • Prohaska, J. R., Downing, S. W., and Lukasewycz, O. A., 1983, Chronic dietary copper deficiency alters biochemical and morphological properties of mouse lymphoid tissues, J. Nutr., 113:1583–1590.

    CAS  Google Scholar 

  • Prohaska, J. R., and Lukasewycz, O. A., 1981, Copper deficiency suppresses the immune response of mice, Science, 213:559–561.

    Article  CAS  Google Scholar 

  • Prohaska, J. R., and Lukasewycz, O. A., 1989, Biochemical and immunological changes in mice following postweaning copper deficiency, Biol. Trace Elem. Res., in press.

    Google Scholar 

  • Prohaska, J.R., Solem, L.E., and Lukasewycz, O.A., 1988a Variation in interleukin-2 (IL-2) production by copper-deficient mice. FASEB J., 2: A436.

    Google Scholar 

  • Prohaska, J. R., and Wells, W. W., 1975, Copper deficiency in the developing rat brain: evidence for abnormal mitochondria, J. Neurochem., 25:221–228.

    Article  CAS  Google Scholar 

  • Prohaska, J. R., Wittmers, L. E., and Haller, E. W., 1988b, Influence of genetic obesity, food intake, and adrenalectomy in mice on selected trace element-dependent protective enzymes, J. Nutr., 118:739–746.

    CAS  Google Scholar 

  • Rosenstreich, D. L., Farrar, J. J., and Dougherty, S., 1976, Absolute macrophage dependency of T lymphocyte activation by mitogens, J. Immunol., 116:131–139.

    CAS  Google Scholar 

  • Roth, R. A., and Koshland, M. E., 1981, Identification of a lymphocyte enzyme that catalyzes pentamer immunoglobulin M assembly, J. Biol. Chem., 256:4633–46539.

    CAS  Google Scholar 

  • Rusinko, N., and Prohaska, J. R., 1985, Adenine nucleotide and lactate levels in organs from copper-deficient mice and brindled mice, J. Nutr., 115:936–943.

    CAS  Google Scholar 

  • Sandstead, H. H., 1982, Copper bioavailability and requirements, Am. J. Clin. Nutr., 35:809–814.

    CAS  Google Scholar 

  • Simon, S. R., Branda, R. F., Tindle, B. H., and Burns, S. L., 1988, Copper deficiency and sideroblastic anemia associated with zinc ingestion, Am. J. Hematol., 28:181–183.

    Article  CAS  Google Scholar 

  • Thomas, W. R., and Holt, P. G., 1978, Vitamin C and immunity: an assessment of the evidence, Clin Exp. Immunol., 32:370–379.

    CAS  Google Scholar 

  • Vyas, E., and Chandra, R. K., 1983, Thymic factor activity, lymphocyte stimulation response and antibody producing cells in copper deficiency, Nutr. Res., 3:343–349.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Biochemistry and Medical Microbiology and Immunology, University of Minnesota, Duluth, Duluth, MN, 55812, USA

    Joseph R. Prohaska & Omelan A. Lukasewycz

Authors
  1. Joseph R. Prohaska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omelan A. Lukasewycz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Hoffmann LaRoche, Inc., Nutley, New Jersey, USA

    Adrianne Bendich

  2. Agricultural Research Service, USDA, NADC, Ames, Iowa, USA

    Marshall Phillips

  3. Colorado State University, Fort Collins, Colorado, USA

    Robert P. Tengerdy

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Plenum Press, New York

About this chapter

Cite this chapter

Prohaska, J.R., Lukasewycz, O.A. (1990). Effects of Copper Deficiency on the Immune System. In: Bendich, A., Phillips, M., Tengerdy, R.P. (eds) Antioxidant Nutrients and Immune Functions. Advances in Experimental Medicine and Biology, vol 262. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0553-8_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0553-8_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-7863-4

  • Online ISBN: 978-1-4613-0553-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation