Skip to main content
PMC home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2000 Apr 19;14(3):91–96. doi: 10.1002/(SICI)1098-2825(2000)14:3<91::AID-JCLA2>3.0.CO;2-O

Influence of cholecalciferol (vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice

Mauro W Vaisberg 1,✉, Ramon Kaneno 2, Marcelo F Franco 3, Nelson F Mendes 4
PMCID: PMC6808021  PMID: 10797606

Abstract

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney. J. Clin. Lab. Anal. 14:91–96, 2000. © 2000 Wiley‐Liss, Inc.

Keywords: lupus nephritis, vitamin D3, hormones, autoimmune disease, ultraviolet radiation

REFERENCES

  • 1. Blalock JE. The syntax of immune‐neuroendocrine communication. Immunol Today 1994;5:504–511. [DOI] [PubMed] [Google Scholar]
  • 2. Reichlin S. Neuroendocrine‐immune interactions. New Engl J Med 1993;329:1246–1253. [DOI] [PubMed] [Google Scholar]
  • 3. Savino W, Dardenne M. Immune‐neuroendocrine interactions. Immunol Today 1995;16:318–322. [DOI] [PubMed] [Google Scholar]
  • 4. Homo‐Delarche F, Durant S. Hormones, neurotransmitters and neuropeptides as modulators of lymphocyte functions In: Rola‐Plesczynski M, editor. Immunopharmacolgy of Lymphocytes. London: Academic Press Limited; 1994. p 169–240. [Google Scholar]
  • 5. Beeson PB. Age and sex associations of 40 autoimmune diseases. Am J Med 1994;96:457–462. [DOI] [PubMed] [Google Scholar]
  • 6. Walker SE, Allen SH, Hoffman RW, McMurray RW. Prolactin, a stimulator of disease activity in systemic lupus erythematosus. Lupus 1995;4(1):3–9. [DOI] [PubMed] [Google Scholar]
  • 7. Blank M, Krause I, Buskila D, et al. Bromocriptin immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells. Cell Immunol 1995;162: 114–122. [DOI] [PubMed] [Google Scholar]
  • 8. Vollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Arthtitis Rheum 1995;38(12):1826–1831. [DOI] [PubMed] [Google Scholar]
  • 9. Fraser DR. Regulation of the metabolism of vitamin D. Physiol Rev 1980;60:551–613. [DOI] [PubMed] [Google Scholar]
  • 10. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas LJ. 1,25‐dihydroxyvitamin D3 receptors in human leucocytes. Science 1983;221:1181–1183. [DOI] [PubMed] [Google Scholar]
  • 11. Lemire JM, Adams JA, Sakai R, Jordan SC. 1 alpha,25‐dihydroxyvitamin D3 suppresses proliferation and immnunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest 1984;74: 657–661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Lemire JM, Adams JS, Kermani‐Arab V, Bakke AC, Sakai R, Jordan SC. 1,25‐dihydroxyvitamin D3 suppressess human T helper/inducer lymphocyte activity in vitro. J Immunol 1985;134:3032–3035. [PubMed] [Google Scholar]
  • 13. Mathieu C. Activated form of vitamin D (1,25(OH)2D3) and its analogs are dose‐reducing agents for cyclosporine in vitro and in vivo. Transplant. Proc 1994;26: 3048–3049. [PubMed] [Google Scholar]
  • 14. Mills JA. Systemic lupus erythematosus. New Engl J Med 1994;330(26): 1871–1879. [DOI] [PubMed] [Google Scholar]
  • 15. Cohen MR, Isenberg A. Ultraviolet irradiation in systemic lupus erythematosus: friend or foe? Br J Rheumatol 1996;35:1002–1007. [DOI] [PubMed] [Google Scholar]
  • 16. Norins LC, Holmes MC. Antinuclear factor in mice. J Immunol 1964;93:148–154. [PubMed] [Google Scholar]
  • 17. Austin HA. Prognostic factors in lupus nephritis. Contribution of histologic data. Am J Med 1983;75:382. [DOI] [PubMed] [Google Scholar]
  • 18. D'Agati VD. Systemic lupus erythematosus In: Silva FG, D'Agati VD, Nadesdy T, editors. Renal biopsy interpretation, London: Churchill Livingstone, 1997. [Google Scholar]
  • 19. Zar JH. Biostatistical analysis, 2nd ed Englewood Cliffs, N.J.: Prentice Hall Inc., 1984. [Google Scholar]
  • 20. Rook GAW, Hernandez‐Pando R, Lightman SL. Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance. Immmunol Today 1994;15:301–303. [DOI] [PubMed] [Google Scholar]
  • 21. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. New Engl J Med 1989;320: 980–991. [DOI] [PubMed] [Google Scholar]
  • 22. Rigby WFC, Denome S, Fanger MW. 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;79:1659–1664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Rigby WFC, Yirinec B, Oldershaw RL, Fanger MW. Comparison of the effects of 1,25‐dihydroxyvitamin D3 on T lymphocyte subpopulation. Eur J Immunol 1987;17:563–566. [DOI] [PubMed] [Google Scholar]
  • 24. Rigby WFC. The immunobiology of vitamin D. Immunol Today 1988;9(2): 54–57. [PubMed] [Google Scholar]
  • 25. Adams JS, Singer FR, Gocadd MA. Isolation and structural identification of 1,25‐dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. J Clin Endocrinol Metab 1985;60:960–966. [DOI] [PubMed] [Google Scholar]
  • 26. Reichel H, Koeffler HP, Barbers R, Norman AW. Regulation of 1,25‐dihydroxivitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. J Clin Endocrinol Metab 1987;65:1201–1209. [DOI] [PubMed] [Google Scholar]
  • 27. Koeffler HP, Reichel H, Bishop JE, Norman AW. Gamma‐interferon stimulates production of 1,25‐dihydroxivitamin D3 by normal human macrophages. Biochem Bioph Res Commun 1985;127:596–603. [DOI] [PubMed] [Google Scholar]
  • 28. Bhalla AK, Armento EP, Clemens TL, Holick MF, Krane SM. Specific high affinity receptors for 1,25 dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 1983; 57(6):1308–1310. [DOI] [PubMed] [Google Scholar]
  • 29. Rigby WFC, Noelle RJ, Krause K, Fanger MW. Effects of 1,25‐dihydroxyvitamin D3 on human T lymphocyte activation and proliferation: a cell cycle analysis. J Immunol 1985;135:2279–2286. [PubMed] [Google Scholar]
  • 30. Bhalla AK, Armento EP, Krane SM. Differential effects of 1,25‐dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophage: inhibition of interleukin‐2 and augmentation of interleukin‐1 production. Cell Immunol 1986;98:311–322. [DOI] [PubMed] [Google Scholar]
  • 31. Daynes RA, Enioutina EY, Butler S, Um HH, McGee ZA, Araneo BA. Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization. Infect Immun 1996;64:1100–1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Koizumi T, Nakao Y, Matsui T, et al. Effects of corticosteroid and 1,24R‐Dihydroxyvitamin D3 administration on lymphoproliferation and autoimmune disease in MRL/MMP‐lpr/lpr mice. Int Arch Allergy Immunol 1985;77:396–404. [DOI] [PubMed] [Google Scholar]
  • 33. Lemire JM, Ince A, Takashima M. 1,25‐Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/I mice.Autoimmunity 1992;12: 143–148. [DOI] [PubMed] [Google Scholar]
  • 34. Holick MF. Photosyntesis, metabolism and biologic actions of vitamin D In: Glorieux SH, editor. Rickets. Nestlé Nutrition Workshop Series 21 New York: Raven Press; 1991. [Google Scholar]
  • 35. Spangler WL, Gribble DH, Lee TC. Vitamin D intoxication and the pathogenesis of vitamin D nephropathy in dog. Am J Vet Res 1979;40:73–83. [PubMed] [Google Scholar]
  • 36. Alarcón‐Riquelme ME, Mollere G, Fernandez C. Macrophage depletion decreases IgG anti‐DNA in cultures from (NZBxW)F1 spleen cells by eliminating the main source of IL‐6. Clin Exp Immunol 1993;91(2): 220–225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Nocker WA, Wigand R, Schoeppe W, Scherberich JE. Elevated levels of soluble CD 14 in serum of patients with systemic lupus erythemtosus. Clin Exp Immunol 1994;96:15–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Szucs G, Kavai M, Suranyi P, Kiss E, Csipo I, Szegedi G. Correlations of monocyte phagocytic receptor expressions with serum immune complex level in systemic lupus erythematosus. Scand J Immunol 1994;40:481–484. [DOI] [PubMed] [Google Scholar]
  • 39. Linker‐Israelli M. Cytokine abnormalities in human lupus. Clin Immunol Immunopathol 1992;63:10–12. [DOI] [PubMed] [Google Scholar]
  • 40. Lemire JM, Archer CD. 1,25‐Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 1991;87: 1103–1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Mathieu C, Waer M, Casteels K, Laureys J, Bouillon R. Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 125‐dihydroxyvitamin D3, KH 1060. Endocrinology 1995;136:866–872. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES