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. 1991 Mar;87(3):1103–1107. doi: 10.1172/JCI115072

1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis.

J M Lemire 1, D C Archer 1
PMCID: PMC329907  PMID: 1705564

Abstract

The hormone, 1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3), inhibits lymphocyte activation in vitro. We studied the ability of the vitamin D metabolite to interfere in vivo with a primary T cell-mediated model of autoimmunity, murine experimental autoimmune encephalomyelitis (EAE). Within 2 wk of antigenic challenge, immunized animals will develop acute paralysis with central nervous tissue inflammation. If mice survive, a rise in antibody titer develops within a month. The administration of 0.1 microgram 1,25-(OH)2-D3 i.p. given every other day for 15 d, starting 3 d before immunization, significantly prevented the development of EAE. The rise in antibody titer to myelin basic protein was also abrogated. Histopathologic lesions of EAE were inhibited by treatment with the sterol. These results suggest a potent immunosuppressive role for 1,25-(OH)2-D3 in vivo in the modulation of a cell-mediated model of autoimmunity.

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Selected References

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  1. Abe J., Takita Y., Nakano T., Miyaura C., Suda T., Nishii Y. A synthetic analogue of vitamin D3, 22-oxa-1 alpha,25-dihydroxyvitamin D3, is a potent modulator of in vivo immunoregulating activity without inducing hypercalcemia in mice. Endocrinology. 1989 May;124(5):2645–2647. doi: 10.1210/endo-124-5-2645. [DOI] [PubMed] [Google Scholar]
  2. Bhalla A. K., Amento E. P., Serog B., Glimcher L. H. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984 Oct;133(4):1748–1754. [PubMed] [Google Scholar]
  3. Eisman J. A., Barkla D. H., Tutton P. J. Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res. 1987 Jan 1;47(1):21–25. [PubMed] [Google Scholar]
  4. Fournier C., Gepner P., Sadouk M., Charreire J. In vivo beneficial effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the induction of experimental autoimmune thyroiditis. Clin Immunol Immunopathol. 1990 Jan;54(1):53–63. doi: 10.1016/0090-1229(90)90005-b. [DOI] [PubMed] [Google Scholar]
  5. Honma Y., Hozumi M., Abe E., Konno K., Fukushima M., Hata S., Nishii Y., DeLuca H. F., Suda T. 1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells. Proc Natl Acad Sci U S A. 1983 Jan;80(1):201–204. doi: 10.1073/pnas.80.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kasukabe T., Honma Y., Hozumi M., Suda T., Nishii Y. Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies. Cancer Res. 1987 Jan 15;47(2):567–572. [PubMed] [Google Scholar]
  7. Lassmann H., Suchanek G., Kitz K., Stemberger H., Schwerer B., Bernheimer H. Antibodies in the pathogenesis of demyelination in chronic relapsing EAE (cr-EAE). Prog Clin Biol Res. 1984;146:165–170. [PubMed] [Google Scholar]
  8. Lemire J. M., Adams J. S., Kermani-Arab V., Bakke A. C., Sakai R., Jordan S. C. 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol. 1985 May;134(5):3032–3035. [PubMed] [Google Scholar]
  9. Lemire J. M., Adams J. S., Sakai R., Jordan S. C. 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest. 1984 Aug;74(2):657–661. doi: 10.1172/JCI111465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lemire J. M., Weigle W. O. Passive transfer of experimental allergic encephalomyelitis by myelin basic protein-specific L3T4+ T cell clones possessing several functions. J Immunol. 1986 Nov 15;137(10):3169–3174. [PubMed] [Google Scholar]
  11. Manolagas S. C., Provvedini D. M., Murray E. J., Tsoukas C. D., Deftos L. J. The antiproliferative effect of calcitriol on human peripheral blood mononuclear cells. J Clin Endocrinol Metab. 1986 Aug;63(2):394–400. doi: 10.1210/jcem-63-2-394. [DOI] [PubMed] [Google Scholar]
  12. Manolagas S. C., Provvedini D. M., Tsoukas C. D. Interactions of 1,25-dihydroxyvitamin D3 and the immune system. Mol Cell Endocrinol. 1985 Dec;43(2-3):113–122. doi: 10.1016/0303-7207(85)90074-7. [DOI] [PubMed] [Google Scholar]
  13. Provvedini D. M., Manolagas S. C. 1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes. J Clin Endocrinol Metab. 1989 Apr;68(4):774–779. doi: 10.1210/jcem-68-4-774. [DOI] [PubMed] [Google Scholar]
  14. Provvedini D. M., Tsoukas C. D., Deftos L. J., Manolagas S. C. 1 alpha,25-Dihydroxyvitamin D3-binding macromolecules in human B lymphocytes: effects on immunoglobulin production. J Immunol. 1986 Apr 15;136(8):2734–2740. [PubMed] [Google Scholar]
  15. Rigby W. F., Denome S., Fanger M. W. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest. 1987 Jun;79(6):1659–1664. doi: 10.1172/JCI113004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rigby W. F., Stacy T., Fanger M. W. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J Clin Invest. 1984 Oct;74(4):1451–1455. doi: 10.1172/JCI111557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rigby W. F. The immunobiology of vitamin D. Immunol Today. 1988 Feb;9(2):54–58. [PubMed] [Google Scholar]
  18. Tsoukas C. D., Provvedini D. M., Manolagas S. C. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science. 1984 Jun 29;224(4656):1438–1440. doi: 10.1126/science.6427926. [DOI] [PubMed] [Google Scholar]
  19. Weigle W. O. Analysis of autoimmunity through experimental models of thyroiditis and allergic encephalomyelitis. Adv Immunol. 1980;30:159–273. doi: 10.1016/s0065-2776(08)60196-0. [DOI] [PubMed] [Google Scholar]
  20. Zhou J. Y., Norman A. W., Chen D. L., Sun G. W., Uskokovic M., Koeffler H. P. 1,25-Dihydroxy-16-ene-23-yne-vitamin D3 prolongs survival time of leukemic mice. Proc Natl Acad Sci U S A. 1990 May;87(10):3929–3932. doi: 10.1073/pnas.87.10.3929. [DOI] [PMC free article] [PubMed] [Google Scholar]

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