Skip to main content
×
×
Home

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

  • Maxine Bonham (a1), Jacqueline M. O'Connor (a1), Bernadette M. Hannigan (a1) and J. J. Strain (a1)
Abstract

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.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      The immune system as a physiological indicator of marginal copper status?
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      The immune system as a physiological indicator of marginal copper status?
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      The immune system as a physiological indicator of marginal copper status?
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Miss M. Bonham, fax +44 2870 324965, email mp.bonham@ulst.ac.uk
References
Hide All
Abbas, KA, Lichtman, AH & Pober, JS (1997) Cellular and Molecular Immunology, 3rd ed. Philadelphia, PA, USA: W.B. Saunders Company.
Allen, LH & Solomons, NW (1984) Absorption and malabsorption of mineral nutrients. In Current Topics in Nutrition and Disease, vol. 12, pp. 199229 [Solomons, NW and Rosenberg, IH, editors]. New York, NY: Alan R Liss Inc.
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, 27592764.
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, 17001709.
Babu, U & Failla, ML (1990 b) Respiratory burst and candidacidal activity of peritoneal macrophages are impaired in copper deficient rats. Journal of Nutrition 120, 16921699.
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, 408412.
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, 283290.
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.
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, 67946797.
Bala, S & Failla, LM (1993) Copper repletion restores the number and function of CD4 cells in copper deficient rats. Journal of Nutrition 123, 991996.
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, 749760.
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, 745753.
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, 12311235.
Blakley, BR & Hamilton, DL (1987) The effect of copper deficiency on the immune response in mice. Drug–Nutrient Interactions 5, 103111.
Boyne, R & Arthur, JR (1981) Effects of selenium and copper deficiency of neutrophil function in cattle. Journal of Comparative Pathology 91, 271276.
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, 417419.
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, 898903.
Castillo-Duran, C & Uauy, R (1988) Copper deficiency impairs growth of infants recovering from malnutrition. American Journal of Clinical Nutrition 47, 710714.
Cordano, A, Baertl, JM & Graham, G (1964) Copper deficiency in humans. Annual Review of Nutrition 34, 324326.
Danks, DM (1988) Copper deficiency in humans. Annual Review of Nutrition 8, 235257.
Department of Health (1991) Dietary reference values for food energy and nutrients for the United Kingdom. LondonHMSO.
Dunlap, WM, James, GW & Hume, DM (1974) Anaemia and neutropenia caused by copper deficiency. Annals of Internal Medicine 80, 470476.
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, 8794.
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, 487496.
Failla, ML & Bala, S (1992) Cellular and biochemical functions of copper in immunity. In Nutrition and Immunology, pp. 129141 [Chandra, RK, editor]. St John's, Newfoundland: ARTS Biomedical Publishers and Distributors.
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, 797812.
Huang, ZL & Failla, ML (2000) Copper deficiency suppresses effector activities of differentiated U937 cells. Journal of Nutrition 130, 15361542.
Heresi, G, Castillo-Duran, C, Munoz, C, Arevalo, M & Schlesinger, L (1985) Phagocytosis and immunoglobulins levels in hypocupremic infants. Nutrition Research 5, 13271334.
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, 192195.
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, 26582668.
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, 257262.
Hopkins, RG & Failla, ML (1997 b) Copper deficiency alters DNA-binding activity of the transcription factor NF-κB. FASEB Journal 11, A362.
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, 596601.
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.
Jones, DG & Suttle, NF (1981) Some effects of copper deficiency on leucocyte function in sheep and cattle. Research in Veterinary Science 31, 151156.
Karimbakas, J, Langkamp-Henken, B & Percival, SS (1998) Arrested maturation of granulocytes in copper deficient mice. Journal of Nutrition 128, 18551860.
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, 151156.
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, 412416.
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, 274282.
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. 207210 [Anke, K, Meissner, D and Mills, LF, editors]. Gersdorf: Varlog Media Touristik.
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, 371382.
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, 9971006.
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, 613620.
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, 233240.
Linder, MC & Hazegh-Azam, M (1996) Copper biochemistry and molecular biology. American Journal of Clinical Nutrition 63, 797S811S.
Lukasewycz, OA & Prohaska, JR (1982) Immunisation against transplantable leukemia impaired in copper deficient mice. Journal of the National Cancer Institute 69, 489493.
Lukasewycz, OA & Prohaska, JR (1983) Lymphocytes from copper deficient mice exhibit decreased mitogen reactivity. Nutrition Research 3, 335341.
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.
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, 644647.
Manser, JI, Crawford, CS, Tyrala, EE, Brodsky, NL & Grover, WD (1980) Serum copper concentrations in sick and well preterm infants. Journal of Paediatrics 97, 795799.
Milne, D (1998) Copper intake and assessment of copper status. American Journal of Clinical Nutrition 67, Suppl., 1041S1045S.
Milne, DB & Johnson, PE (1993) Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clinical Chemistry 39, 883887.
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, 263267.
Mulhern, SA & Koller, LD (1988) Severe or marginal copper deficiency results in a graded reduction in immune status in mice. Journal of Nutrition 118, 10411047.
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, 453461.
National Research Council (1989) Recommended Dietary Allowances, 10th ed., pp. 224230. Washington, DC: National Academy Press.
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, 228457.
Paterson, CR & Burns, J (1988) Copper deficiency in infancy. Journal of Biochemical Nutrition 4, 175190.
Percival, SS (1995) Neutropenia caused by copper deficiency: Possible mechanism of action. Nutrition Reviews 53, 5966.
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, 149154.
Prohaska, JR & Lukasewycz, OA (1989) Biochemical and immunological changes in mice following postweaning copper deficiency. Biological Trace Element Research 22, 101112.
Prohaska, JR & Lukasewycz, OA (1990) Effects of copper deficiency on the immune system. Advances in Experimental Medicine and Biology 262, 123143.
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, 429436.
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, 641649.
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, 495501.
Strain, JJ (2000) Defining optimal copper status in humans: concepts and problems. In Trace Elements in Man and Animals 10, pp. 923928 [Roussel, AM, Anderson, RA and Favier, AC, editors]. New York, NY: Kluver Academic/Plenum Publishers.
Sullivan, JL & Ochs, HD (1978) Copper deficiency and the immune system [letter]. Lancet 2, 686.
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, 317325.
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, 324.
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, 11291134.
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, 658664.
Vyas, E & Chandra, RK (1983) Thymic factor activity, lymphocyte stimulation response and antibody producing cells in copper deficiency. Nutrition Research 3, 343349.
Williams, DM (1983) Copper deficiency in humans. Seminars in Hematology 20, 118128.
Windhauser, MM, Kappel, LC, McClure, J & Hegsted, M (1991) Suboptimal levels of dietary copper vary immunoresponsiveness in rats. Biological Trace Element Research 30, 205217.
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, 161188.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 3
Total number of PDF views: 453 *
Loading metrics...

Abstract views

Total abstract views: 4407 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 26th May 2018. This data will be updated every 24 hours.