Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis

PLoS One. 2015 May 12;10(5):e0125836. doi: 10.1371/journal.pone.0125836. eCollection 2015.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund's Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1 μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150 μg) was co-administered on days 3 and 11. The administration of 1,25(OH)2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH)2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH)2D3 was able to control EAE development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Central Nervous System / metabolism
  • Dendritic Cells / cytology
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Female
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / administration & dosage
  • Myelin-Oligodendrocyte Glycoprotein / therapeutic use*
  • Spleen / metabolism
  • Vitamin D / administration & dosage
  • Vitamin D / therapeutic use*
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*

Substances

  • Interleukin-17
  • Interleukin-6
  • Myelin-Oligodendrocyte Glycoprotein
  • Vitamins
  • Vitamin D

Grants and funding

This work was supported by National Counsel of Technological and Scientific Development (CNPq) grant number 301770/2009-3 to AS. São Paulo Research Foundation (FAPESP) grant # 2011/00465-8 to FCM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.