Vitamin D3 Confers Protection from Autoimmune Encephalomyelitis Only in Female Mice

Abstract

The prevalence of multiple sclerosis (MS) increases significantly with decreasing UV B light exposure, possibly reflecting a protective effect of vitamin D3. Consistent with this theory, previous research has shown a strong protective effect 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis (EAE), an MS model. However, it is not known whether the hormone precursor, vitamin D3, has protective effects in EAE. To address this question, B10.PL mice were fed a diet with or without vitamin D3, immunized with myelin basic protein, and studied for signs of EAE and for metabolites and transcripts of the vitamin D3 endocrine system. The intact, vitamin D3-fed female mice had significantly less clinical, histopathological, and immunological signs of EAE than ovariectomized females or intact or castrated males. Correlating with reduced EAE, the intact, vitamin D3-fed female mice had significantly more 1,25-dihydroxyvitamin D3 and fewer CYP24A1 transcripts, encoding the 1,25-dihydroxyvitamin D3-inactivating enzyme, in the spinal cord than the other groups of mice. Thus, there was an unexpected synergy between vitamin D3 and ovarian tissue with regard to EAE inhibition. We hypothesize that an ovarian hormone inhibited CYP24A1 gene expression in the spinal cord, so the locally-produced 1,25-dihydroxyvitamin D3 accumulated and resolved the inflammation before severe EAE developed. If humans have a similar gender difference in vitamin D3 metabolism in the CNS, then sunlight deprivation would increase the MS risk more significantly in women than in men, which may contribute to the unexplained higher MS incidence in women than in men.