Skip to main content
    • Aa
    • Aa

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)

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 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.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ 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 Dropbox 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 Google Drive account. Find out more about sending content to Google Drive.

      The immune system as a physiological indicator of marginal copper status?
      Available formats
Corresponding author
*Corresponding author: Miss M. Bonham, fax +44 2870 324965, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

JD Arthington , AR Spell , LR Corah & F Blecha (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.

A Baker , L Harvey , G Majsak-Newman , S Fairweather-Tait , A Flynn & K Cashman (1998) Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males. European Journal of Clinical Nutrition 53, 408412.

S Bala & LM Failla (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.

S Bala , ML Failla & JK Lunney (1990) T cell numbers and mitogenic responsiveness of peripheral blood mononuclear cells are decreased in copper deficient rats. Nutrition Research 10, 749760.

R Boyne & JR Arthur (1981) Effects of selenium and copper deficiency of neutrophil function in cattle. Journal of Comparative Pathology 91, 271276.

DM Danks (1988) Copper deficiency in humans. Annual Review of Nutrition 8, 235257.

J Eaton-Evans , WE Mcllrath , WE Jackson , H McCartney & JJ Strain (1996) Copper supplementation and the maintenance of bone mineral density in middle-aged women. Journal of Trace Elements in Experimental Medicine 9, 8794.

G Heresi , C Castillo-Duran , C Munoz , M Arevalo & L Schlesinger (1985) Phagocytosis and immunoglobulins levels in hypocupremic infants. Nutrition Research 5, 13271334.

S Higuchi , M Hirashima , H Nunoi , A Higashi , H Naoe & I Matsuda (1995) Characterization of antineutrophil antibodies in patients with neutropenia associated with nutritional copper deficiency. Acta Haematologica 94, 192195.

V Kishore , N Latman , DW Roberts , JB Barnett & JRJ Sorenson (1984) Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat. Agents Action 14, 274282.

CG Lai , WH Huang , A Askari , Y Wang , N Sarvazyan , LM Klevay & TH Chiu (1994) Differential regulation of superoxide dismutase in copper deficient rat organs. Free Radical Biology and Medicine 16, 613620.

CG Lai , WH Huang , LM Klevay , WT Gunning 3rd & TH Chiu (1996) Antioxidant enzyme gene transcription in copper deficient rat liver. Free Radical Biology and Medicine 21, 233240.

OA Lukasewycz & JR Prohaska (1983) Lymphocytes from copper deficient mice exhibit decreased mitogen reactivity. Nutrition Research 3, 335341.

JI Manser , CS Crawford , EE Tyrala , NL Brodsky & WD Grover (1980) Serum copper concentrations in sick and well preterm infants. Journal of Paediatrics 97, 795799.

DW Montgomery , LK Don , CF Zukosi & M Chvapil (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.

SA Mulhern , AR Vessey , GL Taylor & LE Magruder (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.

CR Paterson & J Burns (1988) Copper deficiency in infancy. Journal of Biochemical Nutrition 4, 175190.

SS Percival (1995) Neutropenia caused by copper deficiency: Possible mechanism of action. Nutrition Reviews 53, 5966.

JR Prohaska , WR Bailey , AM Gross & JJ Korte (1990) Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats. Journal of Nutritional Biochemistry 1, 149154.

JR Prohaska & OA Lukasewycz (1989) Biochemical and immunological changes in mice following postweaning copper deficiency. Biological Trace Element Research 22, 101112.

JR Prohaska & OA Lukasewycz (1990) Effects of copper deficiency on the immune system. Advances in Experimental Medicine and Biology 262, 123143.

JR Prohaska , RA Sunde & KB Zinn (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.

LSF Soderberg , JB Barnett , ML Baker , H Salari & JRJ Sorenson (1987) Copper (II)2(3,5-diisopropylsalicylate)2 accelerated recovery of B and T cell reactivity following irradiation. Scandinavian Journal of Immunology 26, 495501.

NF Suttle & DG Jones (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.

E Turley , A McKeown , MP Bonham , JM O'Connor , C Chopra , LJ Harvey , G Majsak-Newman , SJ Fairweather-Tait , S Bügel , B-M Sandström , E Rock , A Mazur , Y Rayssiguier & JJ Strain (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.

E Vyas & RK Chandra (1983) Thymic factor activity, lymphocyte stimulation response and antibody producing cells in copper deficiency. Nutrition Research 3, 343349.

MM Windhauser , LC Kappel , J McClure & M Hegsted (1991) Suboptimal levels of dietary copper vary immunoresponsiveness in rats. Biological Trace Element Research 30, 205217.

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? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 277 *
Loading metrics...

Abstract views

Total abstract views: 1235 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 28th June 2017. This data will be updated every 24 hours.