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The immune system as a physiological indicator of marginal copper status?

Published online by Cambridge University Press:  09 March 2007

Maxine Bonham ,
Jacqueline M. O'Connor ,
Bernadette M. Hannigan  and
J. J. Strain
Maxine Bonham*
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster at Coleraine BT52 1SA, Northern Ireland, UK
Jacqueline M. O'Connor
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster at Coleraine BT52 1SA, Northern Ireland, UK
Bernadette M. Hannigan
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster at Coleraine BT52 1SA, Northern Ireland, UK
J. J. Strain
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), University of Ulster at Coleraine BT52 1SA, Northern Ireland, UK
*
*Corresponding author: Miss M. Bonham, fax +44 2870 324965, email [email protected]
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Abstract

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Cu appears to have many important functional roles in the body that apparently relate, among others, to the maintenance of immune function, bone health and haemostasis. Some have suggested a role for long-term marginal Cu deficiency in the aetiology of a number of degenerative diseases. Accurate diagnosis of marginal Cu deficiency, however, has remained elusive despite an increased understanding of the biochemistry of Cu and its physiological roles in the body. Traditional markers of Cu status, such as serum Cu and caeruloplasmin protein concentrations are insensitive to subtle changes in Cu status. Cu-containing enzymes, such as Cu–Zn-superoxide dismutase, cytochrome c oxidase and diamine oxidase, may be more reliable but evidence to date is not conclusive. Development of markers sensitive to marginal Cu status is essential before conclusions can be drawn concerning the risks of long-term intake of suboptimal dietary Cu. As Cu appears to be essential for maintenance of immune function, activities of specific immunological markers, altered in Cu deficiency, offer alternatives. This review evaluates a selection of immunological markers that could be considered potentially sensitive markers of marginal Cu status. The indices of immune function reviewed are neutrophil function, interleukin 2 production, blastogenic response to mitogens and lymphocyte subset phenotyping.

Keywords

CopperCopper statusImmune system
Type
Review article
Information
British Journal of Nutrition , Volume 87 , Issue 5 , May 2002 , pp. 393 - 403
Copyright
Copyright © The Nutrition Society 2002

References

Abbas, KA, Lichtman, AH & Pober, JS (1997) Cellular and Molecular Immunology, 3rd ed. Philadelphia, PA, USA: W.B. Saunders Company.Google Scholar
Allen, LH & Solomons, NW (1984) Absorption and malabsorption of mineral nutrients. In Current Topics in Nutrition and Disease, vol. 12, pp. 199–229 [Solomons, NW and Rosenberg, IH, editors]. New York, NY: Alan R Liss Inc.Google Scholar
Arthington, JD, Spell, AR, Corah, LR & Blecha, F (1996) Effect of molybdenum-induced copper deficiency on in vivo and in vitro measures of neutrophil chemotaxis both before and following an inflammatory stressor. Journal of Animal Science 74, 2759–2764.CrossRefGoogle ScholarPubMed
Babu, U & Failla, ML (1990 a) Copper status and function of neutrophils are reversibly depressed in marginally and severely copper-deficient rats. Journal of Nutrition 120, 1700–1709.CrossRefGoogle ScholarPubMed
Babu, U & Failla, ML (1990 b) Respiratory burst and candidacidal activity of peritoneal macrophages are impaired in copper deficient rats. Journal of Nutrition 120, 1692–1699.CrossRefGoogle ScholarPubMed
Baker, A, Harvey, L, Majsak-Newman, G, Fairweather-Tait, S, Flynn, A & Cashman, K (1998) Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males. European Journal of Clinical Nutrition 53, 408–412.CrossRefGoogle Scholar
Baker, A, Turley, E, Bonham, MP, O'Connor, JM, Strain, JJ, Flynn, A & Cashman, KD (1999) No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults. British Journal of Nutrition 82, 283–290.CrossRefGoogle ScholarPubMed
Bala, S, Deshpande, S & Failla, ML (1991 a) Exogenous IL-2 and copper response to in vitro mitogenic reactivity of splenic mononuclear cells from copper deficient rats. FASEB Journal 5, A4095.Google Scholar
Bala, S & Failla, LM (1992) Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity. Proceedings of the National Academy of Science, USA 89, 6794–6797.CrossRefGoogle ScholarPubMed
Bala, S & Failla, LM (1993) Copper repletion restores the number and function of CD4 cells in copper deficient rats. Journal of Nutrition 123, 991–996.Google ScholarPubMed
Bala, S, Failla, ML & Lunney, JK (1990) T cell numbers and mitogenic responsiveness of peripheral blood mononuclear cells are decreased in copper deficient rats. Nutrition Research 10, 749–760.CrossRefGoogle Scholar
Bala, S, Failla, ML & Lunney, JK (1991 b) Alterations in splenic lymphoid cell subsets and activation antigens in copper-deficient rats. Journal of Nutrition 121, 745–753.CrossRefGoogle ScholarPubMed
Bala, S, Lunney, JK & Failla, ML (1992) Effects of copper deficiency on T-cell mitogenic responsiveness and phenotypic profile of blood mononuclear cells from swine. American Journal of Veterinary Research 53, 1231–1235.CrossRefGoogle ScholarPubMed
Blakley, BR & Hamilton, DL (1987) The effect of copper deficiency on the immune response in mice. Drug–Nutrient Interactions 5, 103–111.Google ScholarPubMed
Boyne, R & Arthur, JR (1981) Effects of selenium and copper deficiency of neutrophil function in cattle. Journal of Comparative Pathology 91, 271–276.CrossRefGoogle ScholarPubMed
Boyne, R & Arthur, JR (1986) Effects of molybdenum or iron induced copper deficiency on the viability and function of neutrophils from cattle. Research in Veterinary Science 41, 417–419.CrossRefGoogle ScholarPubMed
Castillo-Duran, C, Fisberg, M, Valenzuela, A, Egana, JI & Uauy, R (1983) Controlled trial of copper supplementation during the recovery from marasmus. American Journal of Clinical Nutrition 37, 898–903.CrossRefGoogle ScholarPubMed
Castillo-Duran, C & Uauy, R (1988) Copper deficiency impairs growth of infants recovering from malnutrition. American Journal of Clinical Nutrition 47, 710–714.CrossRefGoogle ScholarPubMed
Cordano, A, Baertl, JM & Graham, G (1964) Copper deficiency in humans. Annual Review of Nutrition 34, 324–326.Google Scholar
Danks, DM (1988) Copper deficiency in humans. Annual Review of Nutrition 8, 235–257.CrossRefGoogle ScholarPubMed
Department of Health (1991) Dietary reference values for food energy and nutrients for the United Kingdom. LondonHMSO.Google Scholar
Dunlap, WM, James, GW & Hume, DM (1974) Anaemia and neutropenia caused by copper deficiency. Annals of Internal Medicine 80, 470–476.Google ScholarPubMed
Eaton-Evans, J, Mcllrath, WE, Jackson, WE, McCartney, H & Strain, JJ (1996) Copper supplementation and the maintenance of bone mineral density in middle-aged women. Journal of Trace Elements in Experimental Medicine 9, 87–94.3.0.CO;2-E>CrossRefGoogle Scholar
Failla, ML, Babu, U & Seidel, KE (1988) Use of immunoresponsiveness to determine that the dietary requirements for copper in young rats is greater with dietary fructose than dietary starch. Journal of Nutrition 118, 487–496.CrossRefGoogle Scholar
Failla, ML & Bala, S (1992) Cellular and biochemical functions of copper in immunity. In Nutrition and Immunology, pp. 129–141 [Chandra, RK, editor]. St John's, Newfoundland: ARTS Biomedical Publishers and Distributors.Google Scholar
Hart, EB, Steenhock, J, Waddell, J & Elvehjem, CA (1928) Iron in Nutrition VII. Copper as a supplement to iron for hemoglobin binding in the rat. Journal of Biological Chemistry 77, 797–812.CrossRefGoogle Scholar
Huang, ZL & Failla, ML (2000) Copper deficiency suppresses effector activities of differentiated U937 cells. Journal of Nutrition 130, 1536–1542.CrossRefGoogle ScholarPubMed
Heresi, G, Castillo-Duran, C, Munoz, C, Arevalo, M & Schlesinger, L (1985) Phagocytosis and immunoglobulins levels in hypocupremic infants. Nutrition Research 5, 1327–1334.CrossRefGoogle Scholar
Higuchi, S, Hirashima, M, Nunoi, H, Higashi, A, Naoe, H & Matsuda, I (1995) Characterization of antineutrophil antibodies in patients with neutropenia associated with nutritional copper deficiency. Acta Haematologica 94, 192–195.CrossRefGoogle ScholarPubMed
Hopkins, RG & Failla, ML (1995) Chronic intake of a marginally low copper diet impairs in vitro activities of lymphocytes and neutrophils from male rats despite minimal impact on conventional indicators of copper status. Journal of Nutrition 125, 2658–2668.Google ScholarPubMed
Hopkins, RG & Failla, ML (1997 a) Copper deficiency reduced interleukin 2 (IL-2) production and IL-2 mRNA in human T lymphocytes. Journal of Nutrition 127, 257–262.Google ScholarPubMed
Hopkins, RG & Failla, ML (1997 b) Copper deficiency alters DNA-binding activity of the transcription factor NF-κB. FASEB Journal 11, A362.Google Scholar
Hopkins, RG & Failla, ML (1999) Transcriptional regulation of interleukin-2 gene expression is impaired by copper deficiency in Jurkat human T lymphocytes. Journal of Nutrition 129, 596–601.CrossRefGoogle ScholarPubMed
Institute of Medicine (2001) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Food and Nutrition Board. Washington, DC: National Academy Press.Google Scholar
Jones, DG & Suttle, NF (1981) Some effects of copper deficiency on leucocyte function in sheep and cattle. Research in Veterinary Science 31, 151–156.CrossRefGoogle ScholarPubMed
Karimbakas, J, Langkamp-Henken, B & Percival, SS (1998) Arrested maturation of granulocytes in copper deficient mice. Journal of Nutrition 128, 1855–1860.CrossRefGoogle ScholarPubMed
Kehoe, CA, Turley, E, Bonham, MP, O'Connor, JM, McKeown, A, Faughnan, MS, Coulter, JS, Gilmore, WS, Howard, AN & Strain, JJ (2000) Response of putative indices of copper status to copper supplementation in human subjects. British Journal of Nutrition 84, 151–156.CrossRefGoogle ScholarPubMed
Kelley, DS, Daudu, PA, Taylor, PC, Mackey, BE & Turnlund, JR (1995) Effects of low-copper diets on human immune response. American Journal of Clinical Nutrition 62, 412–416.CrossRefGoogle ScholarPubMed
Kishore, V, Latman, N, Roberts, DW, Barnett, JB & Sorenson, JRJ (1984) Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat. Agents Action 14, 274–282.CrossRefGoogle ScholarPubMed
Klevay, LM, Buchet, JP, Bumnker, VW, Clayton, BE, Gobson, RS, Maderios, DM, Moser-Veillon, PBL, Payterson, KY, Taper, LJ & Wolf, WR (1993) Copper in the Western diet (Belgium, Canada, UK, and USA). In Trace Elements in Man and Aminals, pp. 207–210 [Anke, K, Meissner, D and Mills, LF, editors]. Gersdorf: Varlog Media Touristik.Google Scholar
Klevay, LM, Cranfield, WK, Gallagher, SK, Henriksen, LK, Lukaski, HC, Bolonchuk, W, Johnson, LK, Milne, DB & Sandstead, HH (1986) Decreased glucose tolerance in 2 men during experimental copper depletion. Nutrition Reports International 33, 371–382.Google Scholar
Koller, LD, Mulhern, SA, Frankel, NC, Steven, MG & Williams, JR (1987) Immune dysfunction in rats fed a diet deficient in copper. American Journal of Clinical Nutrition 45, 997–1006.CrossRefGoogle ScholarPubMed
Lai, CG, Huang, WH, Askari, A, Wang, Y, Sarvazyan, N, Klevay, LM & Chiu, TH (1994) Differential regulation of superoxide dismutase in copper deficient rat organs. Free Radical Biology and Medicine 16, 613–620.CrossRefGoogle ScholarPubMed
Lai, CG, Huang, WH, Klevay, LM, Gunning, WT 3rd & Chiu, TH (1996) Antioxidant enzyme gene transcription in copper deficient rat liver. Free Radical Biology and Medicine 21, 233–240.CrossRefGoogle ScholarPubMed
Linder, MC & Hazegh-Azam, M (1996) Copper biochemistry and molecular biology. American Journal of Clinical Nutrition 63, 797S–811S.Google ScholarPubMed
Lukasewycz, OA & Prohaska, JR (1982) Immunisation against transplantable leukemia impaired in copper deficient mice. Journal of the National Cancer Institute 69, 489–493.Google ScholarPubMed
Lukasewycz, OA & Prohaska, JR (1983) Lymphocytes from copper deficient mice exhibit decreased mitogen reactivity. Nutrition Research 3, 335–341.CrossRefGoogle Scholar
Lukasewycz, OA & Prohaska, JR (1989) Increased interleukin 1 (IL-1) production and decreased interleukin 2 (IL-2) production in copper deficient mice. FASEB Journal 3, A665.Google Scholar
Lukasewycz, O, Prohaska, JR, Meyer, SM, Schmidtke, JR, Hatfield, SM & Marder, P (1985) Alterations in lymphocyte subpopulations in copper-deficient mice. Infection and Immunity 48, 644–647.CrossRefGoogle ScholarPubMed
Manser, JI, Crawford, CS, Tyrala, EE, Brodsky, NL & Grover, WD (1980) Serum copper concentrations in sick and well preterm infants. Journal of Paediatrics 97, 795–799.CrossRefGoogle ScholarPubMed
Milne, D (1998) Copper intake and assessment of copper status. American Journal of Clinical Nutrition 67, Suppl., 1041S–1045S.CrossRefGoogle ScholarPubMed
Milne, DB & Johnson, PE (1993) Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clinical Chemistry 39, 883–887.CrossRefGoogle ScholarPubMed
Montgomery, DW, Don, LK, Zukosi, CF & Chvapil, M (1974) The effect of zinc and other metals on complement hemolysis of SRBC in vitro. Proceedings of the Society of Experimental Biology and Medicine 145, 263–267.CrossRefGoogle Scholar
Mulhern, SA & Koller, LD (1988) Severe or marginal copper deficiency results in a graded reduction in immune status in mice. Journal of Nutrition 118, 1041–1047.CrossRefGoogle ScholarPubMed
Mulhern, SA, Vessey, AR, Taylor, GL & Magruder, LE (1985) Suppression of antibody response by excess dietary zinc exposure during certain stages of ontogeny. Proceedings of the Society of Experimental Biology and Medicine 180, 453–461.CrossRefGoogle ScholarPubMed
National Research Council (1989) Recommended Dietary Allowances, 10th ed., pp. 224–230. Washington, DC: National Academy Press.Google Scholar
Newberne, PM, Hunt, CE & Young, VY (1968) The role of diet and the reticuloendothelial system in the response of rats to Salmonella typhimurium infection. British Journal of Experimental Pathology 49, 228–457.Google Scholar
Paterson, CR & Burns, J (1988) Copper deficiency in infancy. Journal of Biochemical Nutrition 4, 175–190.Google Scholar
Percival, SS (1995) Neutropenia caused by copper deficiency: Possible mechanism of action. Nutrition Reviews 53, 59–66.CrossRefGoogle Scholar
Prohaska, JR, Bailey, WR, Gross, AM & Korte, JJ (1990) Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats. Journal of Nutritional Biochemistry 1, 149–154.CrossRefGoogle ScholarPubMed
Prohaska, JR & Lukasewycz, OA (1989) Biochemical and immunological changes in mice following postweaning copper deficiency. Biological Trace Element Research 22, 101–112.CrossRefGoogle ScholarPubMed
Prohaska, JR & Lukasewycz, OA (1990) Effects of copper deficiency on the immune system. Advances in Experimental Medicine and Biology 262, 123–143.CrossRefGoogle ScholarPubMed
Prohaska, JR, Sunde, RA & Zinn, KB (1992) Livers from copper deficient rats have lower glutathione peroxidase activity and mRNA levels but normal liver selenium levels. Journal of Nutritional Biochemistry 3, 429–436.CrossRefGoogle Scholar
Reiser, S, Powell, A, Yang, CY & Canary, JJ (1987) Effect of copper intake on blood cholesterol and its lipoprotein distribution in men. Nutrition Reports International 36, 641–649.Google Scholar
Soderberg, LSF, Barnett, JB, Baker, ML, Salari, H & Sorenson, JRJ (1987) Copper (II)2(3,5-diisopropylsalicylate)2 accelerated recovery of B and T cell reactivity following irradiation. Scandinavian Journal of Immunology 26, 495–501.CrossRefGoogle Scholar
Strain, JJ (2000) Defining optimal copper status in humans: concepts and problems. In Trace Elements in Man and Animals 10, pp. 923–928 [Roussel, AM, Anderson, RA and Favier, AC, editors]. New York, NY: Kluver Academic/Plenum Publishers.Google Scholar
Sullivan, JL & Ochs, HD (1978) Copper deficiency and the immune system [letter]. Lancet 2, 686.CrossRefGoogle ScholarPubMed
Suttle, NF & Jones, DG (1986) Copper and disease resistance in sheep: a rare natural confirmation of interaction between a specific nutrient and infection. Proceedings of the Nutrition Society 45, 317–325.CrossRefGoogle ScholarPubMed
Torre, PM, Harmon, RJ, Hemken, RW, Clark, TW, Trammell, DS & Bernice, AS (1996) Mild copper insufficiency depresses blood neutrophil function in dairy cattlez. Journal of Nutritional Immunology 4, 3–24.Google Scholar
Turley, E, McKeown, A, Bonham, MP, O'Connor, JM, Chopra, C, Harvey, LJ, Majsak-Newman, G, Fairweather-Tait, SJ, Bügel, S, Sandström, B-M, Rock, E, Mazur, A, Rayssiguier, Y & Strain, JJ (2000) Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project). Free Radical Biology and Medicine 29, 1129–1134.CrossRefGoogle Scholar
Turnlund, JR, Keen, CL & Smith, RG (1990) Copper status and urinary and salivary copper in young men at 3 levels of dietary copper. American Journal of Clinical Nutrition 51, 658–664.CrossRefGoogle ScholarPubMed
Vyas, E & Chandra, RK (1983) Thymic factor activity, lymphocyte stimulation response and antibody producing cells in copper deficiency. Nutrition Research 3, 343–349.CrossRefGoogle Scholar
Williams, DM (1983) Copper deficiency in humans. Seminars in Hematology 20, 118–128.Google ScholarPubMed
Windhauser, MM, Kappel, LC, McClure, J & Hegsted, M (1991) Suboptimal levels of dietary copper vary immunoresponsiveness in rats. Biological Trace Element Research 30, 205–217.CrossRefGoogle ScholarPubMed
Wolford, ST, Schroer, RA, Gohs, FX, Gallo, PD, Brodeck, M, Falk, HB & Ruhren, R (1986) Reference range data base for serum chemistry and haematology values in laboratory animals. Journal of Toxicology 18, 161–188.Google ScholarPubMed