Immunomodulatory effects of Vitamin D in multiple sclerosis

Abstract

Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple sclerosis. In this study, we measured 1,25 (OH)(2) Vitamin D and 25 (OH) Vitamin D levels in multiple sclerosis patients separated into different clinical subgroups according to disease status. In addition, direct effects of 1,25 (OH)(2) Vitamin D on ex vivo CD4+ T cells and myelin-peptide specific T cell lines were investigated to gain more insight into putative regulatory mechanisms in the disease pathogenesis. One hundred and thirty-two Hispanic patients with clinically definite multiple sclerosis were studied, 58 with relapsing remitting multiple sclerosis during remission, 34 during relapse and 40 primary progressive multiple sclerosis cases. Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH)D(3) and 1,25(OH)(2)D(3), measured by ELISA were significantly lower in relapsing-remitting patients than in controls. In addition, levels in patients suffering relapse were lower than during remissions. In contrast, primary progressive patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2)D(3). Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, Vitamin D receptor expression was induced by 1,25(OH)(2)D(3) in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH)D(3) into biologically active 1,25(OH)(2)D(3), since T cells express alpha1-hydroxylase constitutively. Finally, 1,25(OH)(2)D(3) also increased the expression and biological activity of indoleamine 2,3-dioxygenase, mediating significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these data suggest that 1,25(OH)(2)D(3) plays an important role in T cell homeostasis during the course of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.

Is vitamin D in rheumatoid arthritis a magic bullet or a mirage? The need to improve the evidence base prior to calls for supplementation

“…The potential immunomodulatory properties of vitamin D, through interaction of the 1,25(OH) 2 D-vitamin D receptor transcription factor complex with nuclear vitamin D response element (VDRE) genetic sequences, have been excellently reviewed (17). The general theme in these studies is that vitamin D, via VDREs, regulates the immune response by a variety of mechanisms, such as decreasing antigen presentation (18), inhibiting the proinflammatory Th1 profile (19), and inducing Treg cells (20). Such effects provide a clear theoretical basis for a role of vitamin D deficiency in the development and progression of autoimmune inflammatory conditions.…”

维生素d 在免疫反应和自身免疫性疾病特别是多发性硬化中的作用

“…After MS onset, serum 25(OH)D 3 concentration declines [91] , and hypovitaminosis D is observed throughout the course of the disease, even in a clinically isolated syndrome (CIS) [92][93][94] . Thus, the studies measuring 25(OH)D 3 concentration in patients with MS are uninformative in deciding whether vitamin D can decrease the risk of MS [95,96] . In this case, longitudinal studies based on 25(OH)D 3 concentration before the onset of MS are needed [95] .…”

“…Thus, the studies measuring 25(OH)D 3 concentration in patients with MS are uninformative in deciding whether vitamin D can decrease the risk of MS [95,96] . In this case, longitudinal studies based on 25(OH)D 3 concentration before the onset of MS are needed [95] .…”

“…A nested case-control design to sample an underlying pro- Treg phenotype [97] . The level of 25(OH)D 3 or 1,25(OH) 2 D 3 in the blood is correlated with the suppressive activity of Tregs in MS patients [98,99] , and the number of Tregs is correlated with the serum levels of 25(OH)D 3 and 1,25(OH) 2 D 3 [100] .…”

Serum Vitamin D Levels in Indian Patients with Multiple Sclerosis

“…Hence supplementation has not only been proposed to prevent relapses, but also to attenuate disease activity of MS [8,9]. Vitamin D has been shown to have many immuno-modulatory effects in preventing relapses [10,11]. This sparked the interest in a poor vitamin D exposure as a risk factor for developing MS. No published data is available on vitamin D levels in Indian population with MS and a positive study can definitely have therapeutic effects in a country like ours with a low socio economic status where interferons are beyond the reach of most patients.…”