Is Hypovitaminosis D one of the Environmental Risk Factors for Multiple Sclerosis?

Charles Pierrot-Deseilligny; Jean-Claude Souberbielle

Disclosures

Brain. 2010;133(7):1869-1888. 

In This Article

Experimental Results

Role of 1,25(OH)2D

Experimental autoimmune encephalomyelitis (EAE) is the best experimental model of multiple sclerosis. Although experimental findings in EAE may seem to be of debatable relevance when principally discussing a risk factor for a human disease, they do at least contribute to the rationale involving vitamin D in the immunology of a central inflammatory neurological pathology. Based on more than 20 original studies published between the early 1990s and 2010, it emerges that 1,25(OH)2D has both a preventive and a curative effect in EAE (Lemire and Archer, 1991; Cantorna et al., 1996; Mehan and DeLuca, 2002), this effect requiring the presence of calcium (Cantorna et al., 1999) and possibly existing only in females (if using vitamin D3, probably via a potentiation by oestrogens) (Spach and Hayes, 2005; Nashold et al., 2009), with the involvement of various (not mutually exclusive) immunological mechanisms such as an anti-inflammatory effect (Spach et al., 2004), actions on macrophages (Nashold et al., 2000), on different types of cytokines (Cantorna et al., 1998; Spach et al., 2006; Pedersen et al., 2007) and on regulatory T lymphocyte cells, lymphocytes Th1 and Th2 (Mattner et al., 2000; Muthian et al., 2006). The latter mechanism is favoured by some authors, who suggest that vitamin D positively influences the activity of regulatory T lymphocyte cells, restoring a better ratio between the lymphocytes Th2 (protective) and Th1 (aggressive); the overall effect being a decrease in inflammation (Cantorna, 2006, 2008; Smolders et al., 2008a). It should be noted that this mechanism is analogous to the mechanism of interferon-β, used as an immunomodulator in multiple sclerosis therapy, and that a potentiation exists between the beneficial effects of interferon-β and 1,25(OH)2D analogue used together in EAE (Van Etten et al., 2007). However, it may be that the effects of 1,25(OH)2D in EAE result from other mechanisms.

Possible Specific Effect of UVB, Independent of Vitamin D

It has recently been reported that UVB itself may also have a beneficial effect in EAE that could be independent of the 25(OH)D serum level and vitamin D mechanism, the authors suggesting that this immunological UVB effect could account for the assumed immunological effect of vitamin D previously reported in EAE as well as in multiple sclerosis (Becklund et al., 2010). However, this as yet unique study will need additional confirmation since a transitory significant increase in the 25(OH)D serum level was nevertheless observed in the mice treated with UVB. Furthermore, UVB could have produced 1,25(OH)2D directly in the mouse skin (Lehman et al., 2001; Reichrath, 2007), this finally resulting, via the draining lymph nodes and the general immune system, in a general positive immunosuppressive effect (Gorman et al., 2007; Loser and Beissert, 2009) whatever the 25(OH)D serum level. Lastly, a possible specific action of UVB does not exclude a parallel immunological effect of 1,25(OH)2D in EAE, an effect that has previously been shown in many different studies in which UVB did not play any role (see above and Niino et al., 2008).

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