Copper Complexes Stimulate Hemopoiesis and Lymphopoiesis

  • Lee S. F. Soderberg
  • John B. Barnett
  • J. R. J. Sorenson


Copper(II)2(3,5-diisopropylsalicylate)4[Cu(II)2(3, 5-DIPS)4] is a synthetic copper complex with a variety of effects, including radiation recovery, anti-inflammatory, and accelerated wound healing activities. When C57BL/6 mice were injected subcutaneously with 80 μmol/kg Cu (II) 2(3, 5-DIPS) 4their spleens significantly enlarged. This splenomegally lasted for at least 3 weeks and was accompanied by increased myelopoiesis in the spleen. Bone marrow had no significant change in cellularity or myelopoiesis. The treatment with Cu(II)2(3,5-DIPS)4had only minor effects on the ability of spleen cells to respond to mitogenic or antigenic stimulation. Cu(II)2(3,5-DIPS)4did stimulate lymphopoiesis, since it accelerated the recovery of immune reactivity following exposure to 8 Gy whole body irradiation. Copper levels in the spleens and bone marrow of unirradiated mice treated with Cu(II)2(3,5-DIPS)4were not significantly elevated 24 hr after treatment and copper levels were transiently reduced 7 days after treatment.


Spleen Cell Copper Level Irradiate Mouse Spleen Weight Oxygen Radical Scavenger 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Koller, L.D., S.A. Mulhern, N.C. Frankel, M.G. Steven, J.R. Williams. 1987. Immune dysfunction in rats fed a diet deficient in copper. Amer. J. Clin. Nutr. 45:997–1006.PubMedGoogle Scholar
  2. 2.
    Mulhern, S.A., E.S. Raveche, H.R. Smith, R.B. Lal. 1987. Dietary copper deficiency and autoimmunity in the NZB mouse. Amer. J. Clin. Nutr. 46:1035–1039.PubMedGoogle Scholar
  3. 3.
    Korte, J.J., J.R. Prohaska. 1987. Dietary copper deficiency alters protein and lipid composition of murine lymphocyte plasma membranes. J. Nutr. 117:1076–1084.PubMedGoogle Scholar
  4. 4.
    Elo, H. 1987. An antiproliferative salicylaldoximato type copper(II) chelate as an enhancer of the cytotoxicity of murine spleen cells to tumor cells in vitro. Cancer Lett. 36:333–339.PubMedCrossRefGoogle Scholar
  5. 5.
    Peterson, J. 1987. Inhibition of T cell-dependent antibody production by D-penicillamine. Allergy 42:37–45.CrossRefGoogle Scholar
  6. 6.
    Sorensen, J.R.J. 1976. Some copper chelates and their anti-inflammatory and anti-ulcer activities. Inflamm. 1:317–331.CrossRefGoogle Scholar
  7. 7.
    Soderberg, L.S.F., J.B. Barnett, M.L. Baker, L.W. Chang, H. Salari, J.R.J. Sorenson. 1988. Copper(II)2(3,5-di-isopropylsalicylate)4 stimulates hemopoiesis in normal and irradiated mice. Exp. Hematol. 16:577–580.PubMedGoogle Scholar
  8. 8.
    Soderberg, L.S.F., J.B. Barnett, M.L. Baker, H. Salari, J.R.J. Sorenson. 1987. Copper(II)(3,5-diisopropylsalicylate)2 accelerates recovery of B and T cell reactivity following irradiation. Scand. J. Immunol. 26:495–502.PubMedCrossRefGoogle Scholar
  9. 9.
    Townsend, S.F., J.R.J. Sorenson. 1981. Regeneration of the surgically lesioned gastric mucosa during treatment with copper complexes. In Trace Elements in the Pathogenesis and Treatment of Inflammation. K.D. Rainsford, K. Brune, M.W. Whitehouse, editors. Birkhauser Verlag, Deutschland 389–398.Google Scholar
  10. 10.
    Harris, E.D., B.L. O’Dell. 1974. Copper and oxidases in connective tissue metabolism. Adv. Exp. Med. Biol. 48:267–284.PubMedGoogle Scholar
  11. 11.
    Kensler, T.W, D.M. Bush, W.J. Kozumbo. 1983. Inhibition of tumor promotion by a biomimetic superoxide dismutase. Science 221:75–77.PubMedCrossRefGoogle Scholar
  12. 12.
    Solanki, V., L. Yotti, M.K. Logani, T.J. Slaga. 1984. The reduction of tumor-initiating activity and cell mediated mutagenicity of dimethylbenz(a)anthracene by a copper coordination compound. Carcinogenesis 5:129–131.PubMedCrossRefGoogle Scholar
  13. 13.
    Reiners, J.J.Jr., E. Brott, J.R.J. Sorenson. 1986. Inhibition of benzo(a)pyrene-dependent mutagenesis and cytochrome F-450 reductase activity by copper complexes. Caracinogenesis 7:1729–1732.CrossRefGoogle Scholar
  14. 14.
    Sorenson, J.R.J. 1976. Copper chelates as possible active forms of antiarthritic agents. J. Med. Chem. 19:135–148.PubMedCrossRefGoogle Scholar
  15. 15.
    Metcalf, D. 1971. Antigen-induced proliferation in vitro of bone marrow precursors of granulocytes and macrophages. Immunol 20:727–738.Google Scholar
  16. 16.
    Jadus, M.R., R. Parkman. 1986. The selective growth of murine newborn- derived suppressor cells and their probable mode of action. J. Immunol. 136:783–792.PubMedGoogle Scholar
  17. 17.
    Yeh, N.-H., L.S.F. Soderberg. 1982. Fetal calf serum and 2-mercaptoethanol induce anti-trinitrophenyl antibody production. I. Cross-reactive antigen in fetal calf serum. J. Biol. Response Modif. 1:267–276.Google Scholar
  18. Sorenson, J.R.J., E.G. Melby, P.J. Nord, H.G. Petering. 1973.An evaluation of interferences in the determination of zinc, copper, lead, and cadmium in human hair using atomic absorption spectrophotometry. Arch. Envir. Health 27:36–39.Google Scholar
  19. 19.
    Chaudhri, G., I.A. Clark, N.H. Hunt, W.B. Cowden, R. Ceredig. 1986. Effect of antioxdants on primary alloantigen-induced T cell activation and proliferation. J. Immunol. 137:2646–2652.PubMedGoogle Scholar
  20. 20.
    Gallagher, R.B, A.S.G. Curtis. 1984. The superoxide anion in lymphocyte transformation. Immunol. Letters 8:329–333.CrossRefGoogle Scholar
  21. 21.
    Preisler, H.D., G. Christoff, E. Taylor. 1976. Cryoprotective agents as inducers of erythroleukemic cell differentiation in vitro. Blood 47:363–368.PubMedGoogle Scholar
  22. 22.
    Chaudhri, G., N.H. Hunt, I.A. Clark, R. Ceredig. 1988. Antioxidants inhibit proliferation and cell surface expression of receptors for interleukin-2 and transferrin in T lymphocytes stimulated with phorbol myristate acetate and ionomycin. Cell. Immunol. 115:204–213.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Hag, A., R.A. Clark. 1987. Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. J. Immunol. 139:2406–2413.Google Scholar
  24. 24.
    Lacombe, P., I. Carre, M. Fay, J.-J. Pocidalo. 1988.In vitro 02-induced depression of T and B lymphocyte activation is reversed by diethyldithiocarbamate (DDC) treatment. Immunol. Lett. 18:99–108.PubMedCrossRefGoogle Scholar
  25. 25.
    Meagher, R.C., A.J. Salvado, D.G. Wright. 1988.An analysis of the multilineage production of human hematopoietic progenitors in long-term bone marrow culture: Evidence that reactive oxygen intermediates derived from mature phagocytic cells have a role in limiting progenitor cell self-renewal. Blood 72:273–281.PubMedGoogle Scholar
  26. 26.
    Pioch, Y., M. Gerber. 1985. Restoring capacity of immunomodifiers for radiation-induced inhibition of colony-forming T cells. J. Biol. Response Modif. 4:70–82.Google Scholar
  27. 27.
    Vercellotti, G., D. Stroncek, H.S. Jacob. 1987. Granulocyte oxygen radicals as potential suppressors of hemopoiesis: Potentiating roles of lactoferrin and elastase: Inhibitory role of oxygen radical scavengers. Blood Cells 13:199–206.PubMedGoogle Scholar
  28. 28.
    Petkau, A., W.S. Chelack, E. Palamar, J. Gerrard. 1987.In vitro response of human bone marrow progenitor cells to superoxide radicals. Res. Comm. Chem. Path. Pharm. 57:107–116.Google Scholar
  29. 29.
    Boyle, E., P.C. Freeman, A.C. Goudie, F.R. Morgan, M. Thompson. 1976. The role of copper in preventing gastro-intestinal damage by acidic anti-inflammatory drugs J. Pharm. Pharmac. 28:865–868.CrossRefGoogle Scholar
  30. 30.
    Harrison, J.R., D.P. Rillema, J.H.IV Ham, J.J. Sando. 1986. Inhibition of phorbol ester stimulated interleukin 2 production produced by copper (II) complexes. Cancer Res. 46:5571–575.PubMedGoogle Scholar
  31. 31.
    Moore, R.N., F.J. Pitruzzelo, H.S. Larsen, B.T. Rouse. 1984. Feedback regulation of colony-stimulating factor (CSF-1)-induced macrophage proliferation by endogenous E prostaglandins and interferon-a/b. J. Immunol. 133:541–543.PubMedGoogle Scholar
  32. 32.
    Schwartz, G.N., R. Neta, R.M. Vigneulle, M.L. Patchen, T.J. MacVittie. 1988. Recovery of hematopoietic colony-forming cells in irradiated mice pretreated with interleukin 1 (IL-1). Exp. Hematol. 16:752–757.PubMedGoogle Scholar
  33. 33.
    Neta, R., J.J. Oppenheim. 1988. Cytokines in therapy of radiation injury. Blood 72:1093–1095.PubMedGoogle Scholar
  34. 34.
    Monroy, R.L., R.R. Skelly, P. Taylor, A. Dubois, R.E. Donahue, T.J. MacVittie. 1988. Recovery from severe hematopoietic suppression using recombinant human granulocyte-macrophage colony-stimulating factor. Exp. Hematol. 16:344–348.PubMedGoogle Scholar
  35. 35.
    Neta, R., J.J. Oppenheim, S.D. Douches. 1988. Interdependence of the radioprotective effects of human recombinant interleukin 1a, tumor necrosis factor a, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor. J. Immunol. 140:108–111.PubMedGoogle Scholar
  36. 36.
    Neta, R., S.N. Vogel, J.J. Oppenheim, S.D. Douches. 1986. Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF, and IFN gamma. Lymphokine Res. 5 suppl 1:S105–S110.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Lee S. F. Soderberg
    • 1
  • John B. Barnett
    • 1
  • J. R. J. Sorenson
    • 2
  1. 1.Department of Microbiology and ImmunologyCollege of MedicineLittle RockUSA
  2. 2.Department of Medicinal ChemistryCollege of Pharmacy, University of Arkansas for Medical SciencesLittle RockUSA

Personalised recommendations