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

Immunological Aspects

The immunology of multiple sclerosis is complex and only partly known. The effect of vitamin D on the immune response in general could be an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity (Adorini and Penna, 2008). Macrophages and activated T and B lymphocyte cells contain vitamin D receptors and vitamin D appears to control activation of human T cells (von Essen et al., 2010). Furthermore, whereas it is acknowledged that regulatory T lymphocyte cells and cytokines play major roles in autoimmunity (Bettini and Vignali, 2009), 1,25(OH)2D inhibits in vitro the production of inflammatory cytokines and promotes the development of regulatory T lymphocyte cells expressing cytotoxic T lymphocyte antigen 4 (CTLA-4) and forkhead box P3 (FoxP3), resulting in an anti-inflammatory effect (Jeffery et al., 2009). This confirms different beneficial immunological effects previously reported using 1,25(OH)2D in vitro (Lyakh et al., 2005).

Three major independent immunological studies involving vitamin D in patients with multiple sclerosis were published in 2009, with analogous conclusions. In the first study (132 patients with multiple sclerosis and 53 controls), it was suggested that CD4+ T cell proliferation was inhibited by 1,25(OH)2D and that more cells adopted a regulatory T lymphocyte phenotype (Correale et al., 2009). The second study (n = 26) showed that the number of regulatory T lymphocyte cells was correlated with the serum levels of 25(OH)D and 1,25(OH)2D (Royal et al., 2009). In the third study (n = 29), there was no correlation between the 25(OH)D serum levels and the number of regulatory lymphocyte cells, but the inhibitory activity in vitro of these cells on the (aggressive) Th1 lymphocytes was correlated with the serum level of 25(OH)D, with an additional beneficial effect in interferon-β users (Smolders et al., 2009b), without correlation with 1,25(OH)2D, parathyroid hormone and calcium (Smolders et al., 2010). Moreover, similar results appear to have emerged from two other studies (Sloka et al., 2009; Burton et al., 2010) and tumour growth factor-β1, a cytokine produced by several cell types, including the regulatory T lymphocyte cells, was found to be increased in patients supplemented with 1000 IU/day of vitamin D for 6 months (Mahon et al., 2003). Further studies in patients with multiple sclerosis will probably provide more details on the immunological effects of vitamin D, but the results already reported confirm some experimental findings observed in EAE and show that this vitamin, like interferon-β, influences the number and/or activity of the regulatory T lymphocyte cells. This action could represent a direct intervention in the pathogenesis of the disease and strongly suggests that vitamin D plays an immunmodulatory role in multiple sclerosis.

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