Skip to main content
SpringerLink
Log in

Copper and zinc body levels in inflammation: An overview of the data obtained from animal and human studies

  • Review
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

The development of acute and chronic inflammatory processes induces, in the laboratory animal, a net accumulation of both copper and zinc in many body compartments, the inflammed area included. In rheumatoid arthritis, as well as in animal models, only plasma zinc concentration seems to be significantly correlated with disease severity, while the increase in total plasma copper could be described as an “all or nothing” phenomenon. Moreover, in rheumatoid arthritis, it appears that the disease develops and progresses without being linked to either copper or zinc deficiency conditions.

Thus, it seems reasonable to suggest that a rationale for the use of copper and/or zinc in the treatment of inflammatory disorders can only be drawn from the intrinsic pharmacological properties of such trace elements, rather than from the need for their repletion.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J. R. J. Sorenson,Copper complexes offer a physiological approach to treatment of chronic diseases. InProgress in Medicinal Chemistry. Vol. 26 (Eds. G. P. Ellis and G. B. West) pp. 437–568, Elsevier, Amsterdam 1989.

    Google Scholar 

  2. R. J. Cousins and M. R. Swerdel,Ceruloplasmin and metallothionein induction by zinc and 13-cisretinoic acid in rats with adjuvant inflammation. Proc. Soc. Exp. Biol. Med.179, 168–172 (1985).

    PubMed  Google Scholar 

  3. A. Frigo, L. M. Bambara, E. Concari, M. Marrella, U. Moretti, C. Tambalo, G. P. Velo and R. Milamino,Concerning the potential therapeutic value of zinc in rheumatoid and psoriatic arthritis. InCopper and Zinc in Inflammation. (Eds. R. Milanino, K. D. Rainsford and G. P. Velo) pp. 133–142, Kluwer, Dordrecht 1989.

    Google Scholar 

  4. M. W. Whitehouse, K. D. Rainsford, R. M. Taylor and B. Vernon-Roberts,Zinc monoglycerolate: a slow-release source of zinc with anti-arthritic activity in rats. Agents and Actions31, 47–58 (1990).

    Article  PubMed  Google Scholar 

  5. R. Milanino, K. D. Rainsford and G. P. Velo (Eds.)Copper and Zinc in Inflammation. Kluwer, Dordrecht 1989.

    Google Scholar 

  6. L. M. Kelvay,An appraisal of current human copper nutrition. InInflammatory Diseases and Copper (Ed. J. R. J. Sorenson) pp. 123–132, Humana Press, Clifton, NJ 1982.

    Google Scholar 

  7. K. D. Rainsford,Environmental metal ion perturbations, especially as they affect copper status, are a factor in the etiology of arthritic conditions: An hypothesis. InInflammatory Diseases and Copper. (Ed. J. R. J. Sorenson) pp. 137–143, Humana Press, Clifton, NJ 1982.

    Google Scholar 

  8. P. A. Simkin,Oral zinc sulphate in rheumatoid arthritis. Lancet11, 539–542 (1976).

    Article  Google Scholar 

  9. M. C. Powanda,The role of leukocytes endogeneous mediator (endogenous pyrogen) in inflammation.In Inflammatory Diseases and Copper. (Ed. J. R. J. Sorenson) pp. 31–40, Humana Press, Clifton NJ 1982.

    Google Scholar 

  10. R. Milanino, A. Conforti, L. Franco, M. Marrella and G. P. Velo,Copper and inflammation—a possible rationale for the pharmacological manipulation of inflammatory disorders. Agents and Actions16, 504–513 (1985).

    Article  PubMed  Google Scholar 

  11. R. Milanino, A. Cassini, A. Conforti, L. Franco, M. Marrella, U. Moretti and G. P. Velo,Copper and zinc status during acute inflammation: studies on blood, liver and kidneys metal levels in normal and inflamed rats. Agents and Actions19, 215–223 (1986).

    Article  PubMed  Google Scholar 

  12. D. S. Karabelas,Copper metabolism in the adjuvant-induced arthritic rat. Dissertation, University Microfilms Ann Arbor, MI, Order No 72-31,092. Diss. Abstr. Int. B 1972 33(6), 2776 (1972).

    Google Scholar 

  13. V. Kishore,Effects of adjuvant arthritis on copper, zinc, and iron metabolism in the rat. Res. Commun. Chem. Pathol. Pharmacol.63, 153–156 (1989).

    PubMed  Google Scholar 

  14. V. Kishore, N. Latman, D. W. Roberts, J. B. Barnett and J. R. J. Sorenson,Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat. Agents and Actions14, 274–282 (1984).

    Article  PubMed  Google Scholar 

  15. R. Milanino, U. Moretti, E. Concari, M. Marrella and G. P. Velo,Copper and zinc status in adjuvant arthritic rat: Studies on blood, liver, kidneys, spleen and inflamed paws. Agents and Actions24, 365–376 (1988).

    Article  PubMed  Google Scholar 

  16. J. Néve, J. Fontaine, A. Peretz and J. P. Famey,Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats. Agents and Actions25, 146–155 (1988).

    Article  PubMed  Google Scholar 

  17. J. C. Oliva, M. Castell, J. Queralt and C. Castellotte,Effect of chronic inflammation on copper and zinc metabolism. Rev. Esp. Fisiol.43, 25–31 (1987).

    PubMed  Google Scholar 

  18. A. Koj,Acute-phase reactants and lysosomal enzymes in the blood of rats with experimental inflammation or radiation injury. Folia Biologica18, 274–286 (1970).

    Google Scholar 

  19. A. Marusic, K. Kos, A. Stavljenic and S. Vukicevic,Acute zinc deficiency and trabecular bone loss in rats with talc granulomatosis. Biol. Trace Element Res.29, 165–173 (1991).

    Google Scholar 

  20. R. Milanino, M. Marrella, U. Moretti, E. Concari and G. P. Velo,Copper and zinc status in rats with acute inflammation: focus on the inflamed area. Agents and Actions24, 356–364 (1988).

    PubMed  Google Scholar 

  21. R. S. Pekarek and G. L. Evans,Effect of acute infection and edotoxemia on zinc absorption in the rat. Proc. Soc. Exp. Biol. Med.150, 755–758 (1975).

    PubMed  Google Scholar 

  22. M. C. Powanda, G. L. Cockerell and R. S. Pekarek,Amino acid and zinc movement in relation to protein synthesis early in inflammation. Am. J. Physiol.225, 339–401 (1973).

    Google Scholar 

  23. P. Z. Sobocinski, W. J. Canterbury Jr., E. C. Hauer and F. A. Beall,Induction of hypozincemia and hepatic metallothionein synthesis in hypersensitivity reactions. Proc. Soc. Biol. Med.160, 175–179 (1979).

    Google Scholar 

  24. H. J. Thompson, P. Griminger and J. L. Evans,Apparent increase in the requirement of trace minerals subsequent to severe trauma. Fed. Proc.35, 343 (Abstr. 767) (1976).

    Google Scholar 

  25. M. M. Wintrobe, G. E. Cartwright and C. J. Gubler,Studies on the function and metabolism of copper. J. Nutr.50, 395–419 (1953).

    PubMed  Google Scholar 

  26. B. F. Feldman, C. L. Keen, J. J. Kaneko and T. B. Farver,Anemia of inflammatory disease in the dog: Measurement of hepatic superoxide dismutase, hepatic nonheme iron, copper, zinc, and ceruloplasmin and serum iron, copper, and zinc. Am. J. Vet. Res.42, 1114–1117 (1981).

    PubMed  Google Scholar 

  27. G. L. Fisher,Effects of disease on serum copper and zinc. Values in the beagle. Am. J. Vet. Res.38, 935–940 (1977).

    PubMed  Google Scholar 

  28. K. Ganrot,Plasma protein response in experimental inflammation in the dog. Res. Exp. Med.161, 251–261 (1973).

    Article  Google Scholar 

  29. T. Bieganski, M. Z. Blasinska and J. Kusche,Determination of histaminase (diamine oxidase) activity by o-dianisine test: Interference of ceruloplasmin. Agents and Action7, 85–92 (1977).

    Article  PubMed  Google Scholar 

  30. M. C. McGahan,Copper and aspirin treatment increase the antioxidant activity of plasma. Agents and Actions31, 59–64 (1990).

    Article  PubMed  Google Scholar 

  31. M. C. McGahan, L. N. Fleisherand A. M. Grimes,Effects of copper depletion and D-penicillamine treatment on the ocular inflammatory response. Agents and Actions34, 405–409 (1991).

    Article  PubMed  Google Scholar 

  32. M. Podhradska, D. Podhradsky and J. Andrisina,Effect of inflammation on serum glycoproteins in rabbit. Folia Biologica22, 312–319 (1976).

    PubMed  Google Scholar 

  33. S. C. Sweeney,Alterations in tissue and serum ceruloplasmin concentration associated with inflammation. J. Dental. Res.46 1171–1176 (1967).

    Google Scholar 

  34. B. F. Feldman, J. J. Kaneko and T. B. Farver,Anemia of inflammatory disease in the dog: Clinical characterization. Am. J. Vet. Res.42, 1109–1113 (1981).

    PubMed  Google Scholar 

  35. V. Kishore, V. Boutte and L. Fourcade,Nutritional copper deficiency does not affect sponge granuloma formation in the rat. Biol. Trace Element Res.25, 115–122 (1990).

    Google Scholar 

  36. A. Conforti, L. Franco, R. Milanino and G. P. Velo,Copper and ceruloplasmin (Cp) concentrations during the acute inflammatory process in the rat. Agents and Actions12, 303–307 (1982).

    Article  PubMed  Google Scholar 

  37. P. C. Freeman and P. O'Callaghan,Decreased biovailable copper in rat and human arthritic plasma. A rationale for copper therapy. Br. J. Pharmacol.90 (Proc. Suppl.), 49P (1987).

  38. R. Milanino, A. Conforti, M. E. Fracasso, L. Franco, R. Leone, E. Passarella, G. Tarter and G. P. Velo,Concerning the role of endogenous copper in the acute inflammatory process. Agents and actions9, 581–588 (1979).

    Article  PubMed  Google Scholar 

  39. R. Milanino, E. Passarella and G. P. Velo,Adjuvant arthritis in young copper-deficient rats. Agents and Actions8, 623–628 (1978).

    Article  PubMed  Google Scholar 

  40. R. Milanino, A. Frigo, L. M. Bambara, M. Marrella, U. Moretti, M. Pasqualicchio, D. Biasi, R. Gasperini, L. Mainenti and G. P. Velo,Copper and zinc status in rheumatoid arthritis: Studies on plasma, erythrocytes, and urine, and relationship with disease activity markers and pharmacological treatment. Clin. Exp. Rheumatol. (in press).

  41. M. Webb and K. Cain,Functions of metallothionein. Biochem. Pharmacol.31, 137–142 (1982).

    Article  PubMed  Google Scholar 

  42. A. Conforti, L. Franco, R. Milanino, A. Totorizzo and G. P. Velo,Copper metabolism during acute inflammation: Studies on liver and serum copper concentrations in normal and inflamed rats. Br. J. Pharmacol.79, 45–52 (1983).

    PubMed  Google Scholar 

  43. V. Albergoni, A. Cassini, N. Favero and G. P. Rocco,Effect of penicillamine on some metals and metalloproteins in the rat. Biochem. Pharmacol.24, 1131–1133, (1975).

    Article  PubMed  Google Scholar 

  44. V. Kishore,Effects of copper aspirinate and aspirin on tissue copper, zinc, and iron concentrations following chronic oral treatment in the adjuvant arthritic rat. Biol. Trace Element Res.25, 123–135 (1990).

    Google Scholar 

  45. J. Aaseth, E. Munthe, O. Forre and E. Steinnes,Trace elements in serum and urine of patients with rheumatoid arthritis. Scand. J. Rheumatol.7, 237–240 (1978).

    PubMed  Google Scholar 

  46. M. C. Bacon, P. H. White, D. J. Raiten, N. Craft, S. Margolis, O. A. Levander, M. L. Taylor, R. L. Lipnick and S. Sami,Nutritional status and growth in juvenile rheumatoid arthritis. Seminars Arth. Rheum.20, 97–106 (1990).

    Article  Google Scholar 

  47. D. P. Bajpayee,Significance of plasma copper and caeruloplasmin concentrations in rheumatoid arthritis. Ann. Rheum. Dis.34, 162–165 (1975).

    PubMed  Google Scholar 

  48. Z. Balogh, A. F. El-Ghobarey, G. S. Fell, D. H. Brown, J. Dunlop and G. S. Dick,Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis. Ann. Rheum. Dis.39, 329–332 (1980)

    PubMed  Google Scholar 

  49. J. C. Banford, D. H. Brown, R. A. Hazelton, C. J. Mc Neil, R. D. Sturrock and W. E. Smith,Serum copper and erythrocyte superoxide dismutase in rheumatoid arthritis. Ann. Rheum. Dis.41, 458–462 (1982).

    PubMed  Google Scholar 

  50. R. A. Bonnebrake, J. T. McCall, G. G. Hunder and H. F. Polley,Zinc accumulation in synovial fluid. Mayo clin. Proc.47, 746–750 (1972).

    PubMed  Google Scholar 

  51. M. E. Lahey, C. J. Gubler, G. E. Cartwrightand M. M. Wintrobe,Studies on copper metabolism—VII—Blood copper in pregnancy and various pathological states. J. Clin. Invest.32, 329–337 (1953).

    PubMed  Google Scholar 

  52. U. Moretti, A. Frigo, M. Marrella, G. P. Velo, C. Tambalo, L. M. Bambara and R. Milanino,Copper and zinc in plasma, blood cells and urine of rheumatoid patients. Pharmacol. Res. Commun.20 (suppl. 1) 19–20 (1988).

    Google Scholar 

  53. H. Mussalo-Rauhamaa, Y. T. Konttinen, J. Lehto and V. Honkanen,Predictive clinical and laboratory parameters for serum zinc and copper in rheumatoid arthritis. Ann. Rheum. Dis.47, 816–819 (1988).

    PubMed  Google Scholar 

  54. A. Peretz, J. Nève and J. P. Famaey,Effects of chronic and acute corticosteroid therapy on zinc and copper status in rheumatoid arthritis patients. J. Trace Element Electrolytes Health. Dis.3, 103–108 (1989).

    Google Scholar 

  55. A. Peretz, J. Nève, F. Vertongen and J. P. Famaey,Synovial fluid copper, zinc and selenium in relation to inflammatory parameters in rheumatic diseases. InBiology of Copper Complexes (Ed. J. R. J. Sorenson) pp. 583–589, Humana Press, Clifton, NJ 1987.

    Google Scholar 

  56. W. Pruzanski, M. L. Russel, D. A. Gordon and M. A. Ogryzlo,Serum and synovial fluid proteins in rheumatoid arthritis and degenerative joint diseases. Am. J. Med. Sci.265, 483–490 (1973).

    PubMed  Google Scholar 

  57. P. R. Scudder, W. McMurray, A. G. White and T. L. Dormandy,Synovial fluid copper and related variables in rheumatoid and degenerative arthritis. Ann. Rheum. Dis.37, 71–72 (1978).

    PubMed  Google Scholar 

  58. K. L. G. Svenson, R. Hallgren, E. Johansson and U. Lindh,Reduced zinc in peripheral blood cells from patients with inflammatory connective tissue diseases. Inflammation9, 189–199 (1976).

    Article  Google Scholar 

  59. M. I. V. Jayson, P. Davis, J. T. Whitcherand G. Walters,Serum copper and caeruloplasmin in ankylosing spondylitis, systemic sclerosis, and morphea. Ann. Rheum. Dis.35, 443–445 (1976).

    Google Scholar 

  60. L. Mataran-Perez, J. Gonzalez-Dominguez, M. Rodriguez-Perez, D. Rodrigo, M. Abellen-Perez and D. Salvatierra-Rios,Plasma and intraerythrocytic zinc in rheumatoid arthritis and ankylosing spondylitis. Ann. Intern. Med.6, 629–632 (1989).

    Google Scholar 

  61. J. R. J. Sorenson,Mean serum copper, magnesium and zinc concentrations in active rheumatoid and other degenerative connective tissue diseases. InTrace Substances in Environmental Health, Vol. 11 (Ed. D. D. Hemphill) pp. 15–22, University of Missouri, Columbia, MO 1977.

    Google Scholar 

  62. J. H. Freeland, R. Schwartz, R. J. Cousins and A. C. Burkart,Peridontal disease: Relationship of trace element status. Fed. Proc.35, 262 (Abstr. 314) (1976).

    Google Scholar 

  63. C. C. Ainley, J. Cason, L. K. Carlsson, B. M. Slavin and R. P. H. Thompson,Zinc status in inflammatory bowel disease. Clin. Sci.75, 277–283 (1988).

    PubMed  Google Scholar 

  64. N. A. Kryukova,Index of inhibition of ceruloplasmin activity under the effect of ascorbic acid in vitro, in acute inflammatory process. Lab. Delo31, 153–156 (1972).

    Google Scholar 

  65. L. Matarn-Perez, M. Rodriguez-Perez, J. Gonzalez-Dominguez, D. Rodrigo, A Gonzalez-Utrilla, M. Abellan-Perez and D. Salvatierra-Rios,Zinc in arthrosis and microcrystalline arthritis. Rev. Clin. Esp. 60–62 (1991).

  66. G. Michaelson and K. Ljunghall,Patients with dermatitis herpetiformis, acne psoriasis and Darier's disease have low epidermal zinc concentrations. Acta Derm. Venereol.70, 304–308 (1990).

    PubMed  Google Scholar 

  67. R. S. Pekarek and W. R. Beisel,Redistribution and sequestering of essential trace elements during acute infection. InProc. IX Int. Congr. Nutrition, Mexico, 1972, Vol. 2, pp. 193–198. Karger, Basel 1975.

    Google Scholar 

  68. P. R. Scudder, D. Al-Timini, W. McMurray, A. G. White, B. C. Zoob and T. L. Dormandy,Serum copper and related variables in rheumatoid arthritis. Ann. Rheum. Dis.37, 67–70 (1978).

    PubMed  Google Scholar 

  69. A. Conforti, L. Franco, G. Menegale, R. Milanino, G. Piemonte and G. P. Velo,Serum copper and ceruloplasmin levels in rheumatoid arthritis and degenerative joint disease and their pharmacological implications. Pharmacol. Res. Commun.15, 859–867 (1983).

    PubMed  Google Scholar 

  70. H. Hyora, A-L. Makela, P. Pakarinen, T. Bergman and V. Nanto,Trace elements (copper, zinc and iron) in serum of rheumatic children living in south-western Finland. Acta Pharmacol. Toxicol.59 (Suppl. 7), 403–405 (1986).

    Google Scholar 

  71. A. Lorber, L. S. Cutler and C. C. ChangSerum copper levels in rheumatoid arthritis: Relationship of elevated copper to protein alteration. Arch. Rheum.11, 65–71 (1968).

    Google Scholar 

  72. D. H. Brown, W. W. Buchanan, A. F. El-Gobarey, W. E. Smith and J. Teape,Serum copper and its relationship to clinical symptoms in rheumatoid arthritis. Ann. Rheum. Dis.38, 174–176 (1979).

    PubMed  Google Scholar 

  73. A. A. R. Youssef, B. Wood and D. N. Baron,Serum copper: A marker of disease activity in rheumatoid arthritis. J. Clin. Pathol.36, 14–17 (1983).

    PubMed  Google Scholar 

  74. V. Honkanen, P. Pelkonen, H. Mussalo-Rauhamaa, J. Lehto and T. Westermarck,Serum trace elements in juvenile chronic arthritis. Clin. Rheumatol.8, 64–70 (1989).

    Article  PubMed  Google Scholar 

  75. R. Milanino, S. Mazzoli, E. Passarella, G. Tarter and G. P. Velo,Carrageenan oedema in copper deficient rats. Agents and Actions8, 618–622 (1978).

    Article  PubMed  Google Scholar 

  76. N. W. Solomons,Zinc and copper in human nutrition. InZinc and Copper in Medicine. (Eds. Z. A. Kargiogu and R. M. Sarper) pp. 224–275, Charles C. Thomas, Springfield, IL 1980.

    Google Scholar 

  77. R. J. Cousins,Absorption, transport, and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin. Physiol. Rev.65, 238–309 (1985).

    PubMed  Google Scholar 

  78. R. A. Di Silvestro and R. J. Cousins,Physiological ligands for. copper and zinc. Annu. Rev. Nutr.3, 261–288 (1983).

    Article  PubMed  Google Scholar 

  79. R. M. Russel,Vitamin A and zinc metabolism in alcoholism. Am. J. Clin. Nutr.33, 2741–2749 (1980).

    PubMed  Google Scholar 

  80. J. W. Foote and H. T. Delves, Albumin bound and α2-macroglobulin bound zinc concentrations in the sera of healthy adults.. J. Clin. Pathol.37, 1050–1054 (1984).

    PubMed  Google Scholar 

  81. A. S. Prasad,Deficiency of zinc in man and its toxicity. InTrace Elements in Human Health and Disease (Ed. A. S. Prasad) pp. 1–20, Academic Press, New York 1976.

    Google Scholar 

  82. A. S. Prasad,The role of zinc in gastrointestinal and liver disease. InClinics in Gastroenterology (Ed. M. S. Losowsky) pp. 713–741, Saunders, London 1983.

    Google Scholar 

  83. J. Patrick and C. Dervish,Leukocyte zinc in the assessment of zinc status. Crit. Rev. Lab. Sci.20, 95–114, (1984).

    Google Scholar 

  84. W. A. Briggs, M. M. Pedersen, S. K. Mahajan, D. H. Sillix, A. S. Prasad and F. D. McDonald,Lymphocyte and granulocyte function in zinc-treated and zinc-deficient hemodialysis patients. Kidney Int.21, 827–832 (1982).

    PubMed  Google Scholar 

  85. S. Bro, M. Stokholm and P. J. Jørgensen,Zinc in mononuclear leucocytes in alcoholics with liver cirrhosis or chronic pancreatitis and in patients with Crohn's disease before and after zinc supplementation. J. Trace. Element Electrolytes Health Dis.3, 243–248 (1989).

    Google Scholar 

  86. A. Peretz, J. Nève, O. Jechers, N. Leclercq., J.-P. Praet, F. Vertongen and J.-P. Famaey,Interest of zinc determination in leucocyte fractions for the assessment of marginal zinc status. Clin. Chim. Acta203, 35–46 (1991).

    Article  PubMed  Google Scholar 

  87. H. Elling, S. Kiilerich, C. Chritiansen and J. Gylding-Sabroe,The effect of indomethacin and naproxen on zinc metabolism. Scand. J. Rheumatol.7, 145–146 (1978).

    Google Scholar 

  88. M. K. Song and N. F. Adham,Role of prostaglandin E 2 in zinc absorption in the rat. Am. J. Physiol.234, E99-E105 (1978).

    PubMed  Google Scholar 

  89. K. T. Smith, R. J. Cousins, B. L. Silbon and M. L. Failla,Zinc absorption and metabolism by isolated, vascularly perfused rat intestine. J. Nutr.108, 1849–1857 (1978).

    PubMed  Google Scholar 

  90. J. Fontaine, J. Nève, A. Peretz, F. Pelen and J. P. Famaey,Comparison of effects of chronic inflammation and longterm prednisolone administration on zinc metabolism in rats. Int. J. Tissue React.11, 253–259 (1989).

    PubMed  Google Scholar 

  91. J. M. Walshe,Penicillamine. A new oral therapy for Wilson's disease. Am. J. Med.21, 487–495 (1956).

    Article  PubMed  Google Scholar 

  92. V. Albergoni, N. Favero and G. P. Rocco,Copper metabolism in the rat: Effects of copper loading and copper depletion. Bioinorg. Chem.9, 431–440 (1978).

    Article  Google Scholar 

  93. G. J. Brewer, G. M. Hill, A. S. Prasad, Z. T. Cossack and P. Rabbani,Oral Zinc therapy for Wilson's disease. Ann. Intern. Med.99, 314–320 (1983).

    PubMed  Google Scholar 

  94. L. V. Jepsen and K. H. Pedersen,Changes in zinc and zinc-dependent enzymes in rheumatoid patients during penicillamine treatment. Scand. J. Rheumatol.13 282–288 (1984).

    PubMed  Google Scholar 

  95. K. Bibow, B. Salbu, K. M. H. Strand and E. Munthe,The influence of D-penicillamine on trace element excretion. Acta Pharmacol. Toxicol.59 (Suppl. 7), 374–377 (1986).

    Google Scholar 

  96. R. P. Sharma,Metabolism of intracellular zinc and copper following single and repeated injections of gold sodium thiomalate. Agents and Actions13, 380–388 (1983).

    Article  PubMed  Google Scholar 

  97. M. Cutolo, S. Rovida, E. Samanta and S. Accardo,Effect of drugs on serum copper and its correlation with other humoral factors in rheumatoid arthritis. InInflammation: Mechanisms and Treatment. (Eds. D. A. Willoughby and J. P. Giroud) pp. 451–456, MTP Press, Lancaster 1980.

    Google Scholar 

  98. W. E. Smith, D. H. Brown, J. Dunlop, R. Hazelton, R. D. Sturrock and A. J. Lewis,The effect of therapeutic agents on serum copper levels and serum oxidase activities in the rat adjuvant model compared to analogous results from studies of rheumatoid arthritis in humans. InInflammation: Mechanisms and Treatment (Eds. D. A. Willoughby and J. P. Giroud) pp. 457–463, MTP press, Lancaster 1980.

    Google Scholar 

  99. H. Elling, S. Kiilerich, J. Sabro and P. Elling,Influence of a non-steroid antirheumatic drug on serum and urinary zinc in healthy volunteers. Scand. J. Rheumatol. 9, 161–163 (1980).

    PubMed  Google Scholar 

  100. A. Peretz, J. Nève and J. P. Famaey,Zinc, copper and selenium in chronic and acute inflammatory rheumatic diseases. InTrace Element Analytical Chemistry in Medicine and Biology. (Eds. P. Bratter and P. Schramel) pp. 471–476, Walter de Gruyter, Berlin 1988.

    Google Scholar 

  101. J. Fontaine, J. Nève A. Peretz,P. Capel and J. P. Famaey,Effects of acute and chronic prednisolone treatment on serum zinc levels in rats with adjuvant arthritis. Agents and Actions33, 247–253 (1991).

    Article  PubMed  Google Scholar 

  102. G. C. Sturniolo, A. Martin, G. Gurrieri and R. Naccarato,The effects of prostaglandin synthetase inhibition on the oral zinc tolerance test in man. Gastroenterol. Clin. Biol.7, 933, (1983).

    PubMed  Google Scholar 

  103. C. A. Dinarello,Interleukin-l and interleukin-l antagonism. Blood77, 1627–1652 (1991).

    PubMed  Google Scholar 

  104. K. Arai, F. Lee, A. Miyajima, S. Miyatake,N. Arai and T. Yokota,Cytokines: Coordinators of immune and inflammatory responses. Annu. Rev. Biochem.59, 783–836 (1990).

    Article  PubMed  Google Scholar 

  105. I. Paegelow, H. Werner and G. Vietinghoff,The production of interleukin-l induced by an acute non-specific inflammation in mice. Agents and Actions23, 79–81 (1988).

    Article  PubMed  Google Scholar 

  106. M. Perretti, E. Solito and L. Parente,Evidence that endogenous interleukin-l is involved in leukocyte migration in acute experimental inflammation in rats and mice. Agents and Actions35, 71–78 (1992).

    Article  PubMed  Google Scholar 

  107. M. E. Davies, H. Sharma and R. Pigott,ICAM-l expression on chondrocytes in rheumatoid arthritis: induction by synovial cytokines. Mediators Inflammation1, 71–74 (1992).

    Google Scholar 

  108. Y. Iigo, T. Takashi, T. Tamatani, M. Miyasaka, T. Higashida, H. Yagita K. Okumura and W. Tsukada,ICAM-1-dependent pathway is critically involved in the pathogenesis of adjuvant arthritis in rats. J. Immunol.147, 4167–4171 (1991).

    PubMed  Google Scholar 

  109. P. Z. Sobocinski, W. J. Canterbury Jr., C. A. Mapes, R. E. Dinterman, E. C. Hauer and F. B. Abeles,Hypozincemia of inflammation: Sequestration of zinc by hepatic metallothionein. Fed. Proc.37, 890 (Abstract 3558) (1978).

    Google Scholar 

  110. O. J. Hartmann, T. Schechinger and U. Weser,Copperthionein in leucocytes. Biol. Met.2, 40–44 (1989).

    Article  PubMed  Google Scholar 

  111. O. J. Mesna, I. L. Steffensen, A. Melhuus, H. Hjertholm, H. E. Heier and R. A. Andersen,Induction of metallothionein production of zinc in human mononuclear cells. Gen. Pharmacol.21, 909–917 (1990).

    PubMed  Google Scholar 

  112. J. J. Schroeder and R. J. Cusins,Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Proc. Natl. Acad. Sci. USA87, 3137–3141 (1990).

    PubMed  Google Scholar 

  113. R. J. Cousins and A. S. Leinart,Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 2, 2884–2890 (1988).

    PubMed  Google Scholar 

  114. E. J. Lewis, A. D. Sedgwick and T. H. P. Hanahoe,In Vivo changes in plasma acute phase protein levels in the rat induced by slow release of IL-1, IL-6 and TNF. Mediators Inflammation1, 39–44 (1992).

    Google Scholar 

  115. R. A. Di Silvestro and J. T. Marten,Effects of inflammation and copper intake on rat liver and erythrocyte Cu−Zn superoxide dismutase activity levels. J. Nutr.120, 1223–1227 (1990).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Farmacologia, Università di Verona, Policlinico Borgo Roma, I-37134, Verona, Italy

    Roberto Milanino, Mauro Marrella, Roberta Gasperini, Mara Pasqualicchio & Giampaolo Velo

Authors
  1. Roberto Milanino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mauro Marrella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Gasperini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mara Pasqualicchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giampaolo Velo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Milanino, R., Marrella, M., Gasperini, R. et al. Copper and zinc body levels in inflammation: An overview of the data obtained from animal and human studies. Agents and Actions 39, 195–209 (1993). https://doi.org/10.1007/BF01998974

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01998974

Keywords

Search

Navigation