Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Nov 1;160(5):1532–1543. doi: 10.1084/jem.160.5.1532

Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent

PMCID: PMC2187509  PMID: 6333485

Abstract

Lewis rats that are primed with guinea pig spinal cord homogenized in complete Freund's adjuvant (GPSCH-CFA) develop overt symptoms of experimental allergic encephalomyelitis (EAE). Treatment with the iron- chelating agent, desferrioxamine B mesylate (DFOM), at various times before the onset of EAE, dramatically suppressed both the severity and duration of disease. When DFOM was administered to rats soon after the development of neurological signs, a rapid recovery occurred, though mild, transient symptoms could be seen approximately 1 wk after withdrawal of the drug. Treatment with DFOM was always accompanied by a diminution of T cell responsiveness on the part of the delayed-type hypersensitivity/helper subset and, on histological examination, an absence of inflammatory cells from lesions. Iron is believed to influence both the migration and function of immune effector cells. It can also act as a catalyst in the formation of free radicals, which are highly toxic agents causing tissue damage in sites of inflammation. The mechanisms underlying the effect of DFOM on the severity of EAE, and the possible implications for treatment of multiple sclerosis are discussed.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernard C. C., Mackay I. R. Transfer of murine experimental autoimmune encephalomyelitis and cell-mediated immunity to myelin protein is effected by Lyt-1 cells. J Neuroimmunol. 1983 Feb;4(1):61–65. doi: 10.1016/0165-5728(83)90064-4. [DOI] [PubMed] [Google Scholar]
  2. Brosnan C. F., Bornstein M. B., Bloom B. R. The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. J Immunol. 1981 Feb;126(2):614–620. [PubMed] [Google Scholar]
  3. Brosnan C. F., Wisniewski H. M. Immunopathology of allergic encephalomyelitis. Prog Clin Biol Res. 1980;39:379–390. [PubMed] [Google Scholar]
  4. Brown D. J., Dawborn J. K., Ham K. N., Xipell J. M. Treatment of dialysis osteomalacia with desferrioxamine. Lancet. 1982 Aug 14;2(8294):343–345. doi: 10.1016/s0140-6736(82)90544-x. [DOI] [PubMed] [Google Scholar]
  5. Craelius W., Jacobs R. M., Jones A. O. Mineral composition of brains of normal and multiple sclerosis victims. Proc Soc Exp Biol Med. 1980 Nov;165(2):327–329. doi: 10.3181/00379727-165-40980. [DOI] [PubMed] [Google Scholar]
  6. Craelius W., Migdal M. W., Luessenhop C. P., Sugar A., Mihalakis I. Iron deposits surrounding multiple sclerosis plaques. Arch Pathol Lab Med. 1982 Aug;106(8):397–399. [PubMed] [Google Scholar]
  7. De Sousa M. Lymphoid cell positioning: a new proposal for the mechanism of control of lymphoid cell migration. Symp Soc Exp Biol. 1978;32:393–410. [PubMed] [Google Scholar]
  8. Farram E., Geczy C. L., Moon D. K., Hopper K. The ability of lymphokine and lipopolysaccharide to induce procoagulant activity in mouse macrophage cell lines. J Immunol. 1983 Jun;130(6):2750–2756. [PubMed] [Google Scholar]
  9. Fillet G., Cook J. D., Finch C. A. Storage iron kinetics. VII. A biologic model for reticuloendothelial iron transport. J Clin Invest. 1974 Jun;53(6):1527–1533. doi: 10.1172/JCI107703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Geczy C. L., Meyer P. A. Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity. J Immunol. 1982 Jan;128(1):331–336. [PubMed] [Google Scholar]
  11. Halliwell B. Production of superoxide, hydrogen peroxide and hydroxyl radicals by phagocytic cells: a cause of chronic inflammatory disease? Cell Biol Int Rep. 1982 Jun;6(6):529–542. doi: 10.1016/0309-1651(82)90175-8. [DOI] [PubMed] [Google Scholar]
  12. Joynson D. H., Walker D. M., Jacobs A., Dolby A. E. Defect of cell-mediated immunity in patients with iron-deficiency anaemia. Lancet. 1972 Nov 18;2(7786):1058–1059. doi: 10.1016/s0140-6736(72)92340-9. [DOI] [PubMed] [Google Scholar]
  13. KEBERLE H. THE BIOCHEMISTRY OF DESFERRIOXAMINE AND ITS RELATION TO IRON METABOLISM. Ann N Y Acad Sci. 1964 Oct 7;119:758–768. doi: 10.1111/j.1749-6632.1965.tb54077.x. [DOI] [PubMed] [Google Scholar]
  14. Mackay I. R., Carnegie P. R., Coates A. S. Immunopathological comparisons between experimental autoimmune encephalomyelitis and multiple sclerosis. Clin Exp Immunol. 1973 Dec;15(4):471–482. [PMC free article] [PubMed] [Google Scholar]
  15. McCord J. M., Day E. D., Jr Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex. FEBS Lett. 1978 Feb 1;86(1):139–142. doi: 10.1016/0014-5793(78)80116-1. [DOI] [PubMed] [Google Scholar]
  16. Modell C. B., Beck J. Long-term desferrioxamine therapy in thalassemia. Ann N Y Acad Sci. 1974;232(0):201–210. doi: 10.1111/j.1749-6632.1974.tb20586.x. [DOI] [PubMed] [Google Scholar]
  17. Mokhtarian F., McFarlin D. E., Raine C. S. Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature. 1984 May 24;309(5966):356–358. doi: 10.1038/309356a0. [DOI] [PubMed] [Google Scholar]
  18. Panitch H. S., Ciccone C. Adoptive transfer of experimental allergic encephalomyelitis: requirement for macrophages in activation of spleen cells in vitro by concanavalin A or myelin basic protein. Cell Immunol. 1981 May 1;60(1):24–33. doi: 10.1016/0008-8749(81)90244-6. [DOI] [PubMed] [Google Scholar]
  19. Paterson P. Y. Experimental allergic encephalomyelitis: role of fibrin deposition in immunopathogenesis of inflammation in rats. Fed Proc. 1976 Nov;35(13):2428–2434. [PubMed] [Google Scholar]
  20. Peters G., Keberle H., Schmid K., Brunner H. Distribution and renal excretion of desferrioxamine and ferrioxamine in the dog and in the rat. Biochem Pharmacol. 1966 Jan;15(1):93–109. doi: 10.1016/0006-2952(66)90114-6. [DOI] [PubMed] [Google Scholar]
  21. Pettinelli C. B., McFarlin D. E. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. J Immunol. 1981 Oct;127(4):1420–1423. [PubMed] [Google Scholar]
  22. Robbins E., Pederson T. Iron: its intracellular localization and possible role in cell division. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1244–1251. doi: 10.1073/pnas.66.4.1244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SHODEN A., STURGEON P. Iron storage, IV. Cellular distribution of excess liver iron. Am J Pathol. 1962 Jun;40:671–683. [PMC free article] [PubMed] [Google Scholar]
  24. Sriram S., Solomon D., Rouse R. V., Steinman L. Identification of T cell subsets and B lymphocytes in mouse brain experimental allergic encephalitis lesions. J Immunol. 1982 Oct;129(4):1649–1651. [PubMed] [Google Scholar]
  25. Summers M. R., Jacobs A., Tudway D., Perera P., Ricketts C. Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br J Haematol. 1979 Aug;42(4):547–555. doi: 10.1111/j.1365-2141.1979.tb01167.x. [DOI] [PubMed] [Google Scholar]
  26. Traugott U., Shevach E., Chiba J., Stone S. H., Raine C. S. Acute experimental autoimmune encephalomyelitis: T- and B-cell distribution within the target organ. Cell Immunol. 1982 Jul 1;70(2):345–356. doi: 10.1016/0008-8749(82)90335-5. [DOI] [PubMed] [Google Scholar]
  27. Trotter J., Steinman L. Homing of Lyt-2+ and Lyt-2- T cell subsets and B lymphocytes to the central nervous system of mice with acute experimental allergic encephalomyelitis. J Immunol. 1984 Jun;132(6):2919–2923. [PubMed] [Google Scholar]
  28. Willmore L. J., Rubin J. J. Formation of malonaldehyde and focal brain edema induced by subpial injection of FeCl2 into rat isocortex. Brain Res. 1982 Aug 19;246(1):113–119. doi: 10.1016/0006-8993(82)90147-0. [DOI] [PubMed] [Google Scholar]
  29. Wiśniewski H. M. Immunopathology of demyelination in autoimmune diseases and virus infections. Br Med Bull. 1977 Jan;33(1):54–59. doi: 10.1093/oxfordjournals.bmb.a071397. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES