BACKGROUND: Vitamin D deficiency has been implicated as a risk factor for MS, but how vitamin D metabolism affects MS pathophysiology is not understood.
OBJECTIVE: This group studied the expression of vitamin D receptor (VDR) and related enzymes, including 1,25(OH)2D-24-hydroxylase (24-OHase; CYP24A1) and 25(OH)D-1α-hydroxylase (CYP27B1), in CNS tissues of 39 MSers and 20 controls and in primary human glial cells in vitro.
METHODS & RESULTS: In control and MS normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed in oligodendrocyte-like cells, humanleukocyte antigen (HLA)-positive microglia, and glial fibrillary acidic protein-positive astrocytes. There was a 2-fold increase in VDR transcripts in MS NAWM versus control white matter (p = 0.03). In chronic active MS lesions, HLA-positive microglia/macrophages showed nuclear VDR staining; astrocytes showed nuclear and cytoplasmic VDR staining. Staining for 24-OHase was restricted to astrocytes.VDR and CYP27B1 mRNA expressions were increased in active MS lesions versus NAWM (p < 0.01, p = 0.04, respectively). In primary human astrocytes in vitro, the active form of vitamin D, 1,25(OH)2D3, induced upregulation of VDR and CYP24A1. Tumor necrosis factor and interferon-γ upregulated CYP27B1 mRNA in primary human microglia and astrocytes.
CONCLUSIONS: Increased VDR expression in MS NAWM and inflammatory cytokine-induced amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the suppression of active MS lesions.
“Is this cause of effect? Does vD deficiency result in the upregulation of vD receptors and related pathways in the brains of MSers or does these pathways consume vD and result in low levels. The latter could be a called a consumptive vitaminopathy. Chicken or Egg? Is it important? Yes, the evidence suggests vD has a complex role to play in inflammation; therefore vD deficiency may result in an aberrant immune response that drive autoimmune reactions. Supplementing vD may therefore suppress or turn off inflammation. Unfortunately, we don’t have the data to support the latter at present. My take on this is that you need to be vD replete anyway; your bones need it. If the vD helps suppress inflammation then you have done no harm.”