Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS

Stewart, Niall; Simpson, Steve; Mei, Ingrid van der; Ponsonby, Anne–Louise; Blizzard, Leigh; Dwyer, T; Pittas, Fotini; Eyles, Darryl W.; Ko, Pauline; Taylor, Bruce

doi:10.1212/wnl.0b013e31825fded9

Cited by 89 publications

(74 citation statements)

References 26 publications

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“…In contrast to these inconclusive small controlled studies, several recent association studies found a significant relationship between the vitamin D status and the relapse rate in patients with RRMS [Smolders et al 2008b;Runia et al 2012], with possible variable positive or negative interactions with IFNβ depending upon the vitamin D serum level, higher or lower than 50 nmol/liter respectively [Stewart et al 2012]. In another recent association study, preliminary results provided evidence that low serum 25-OH-D levels are an important risk factor for conversion from CIS to MS, suggesting that vitamin D supplementation in combination with IFNβ-1b may improve outcomes in CIS [Ascherio et al 2012b].…”

Section: Relapsesmentioning

confidence: 84%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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Abstract:The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.

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Section: Relapsesmentioning

confidence: 84%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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“…It has been suggested that IFN-b and vitamin D may interact and exert a synergistic immunomodulatory effect. 36,37 Our sample size was not powered to investigate this possible interaction; however, the proportion of patients treated with IFN-b was similar in the 2 treatment arms, thus eliminating possible confounding of this study's findings. In the high-dose group, a more pronounced immunologic effect of cholecalciferol was observed in a subset of patients; however, this study was not powered to perform subgroup analyses and this should be further investigated in future studies.…”

Section: Cd4mentioning

confidence: 99%

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

et al. 2016

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Objective: To study the safety profile and characterize the immunologic effects of high-vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).Methods: In this double-blind, single-center randomized pilot study, 40 patients with relapsingremitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months.Results: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the lowdose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17T cells (p 5 0.03), and effector memory CD4 1 T cells (p 5 0.021) with a concomitant increase in the proportion of central memory CD41 T cells (p 5 0.018) and naive CD4 1 T cells (p 5 0.04). These effects were not observed in the low-dose group.Conclusions: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD41 T cells and decreased proportion of effector memory CD41 T cells with concomitant increase in central memory CD4 1 T cells and naive CD4 1 T cells. Classification of evidence:This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects. 6,7 These observations may reflect the pleiotropic immunomodulatory effects of vitamin D, involving the innate and adaptive immune system. 7-9The majority of studies examining the immunologic effects of vitamin D have been conducted either in vitro or in animal models, and human studies have employed differing methods and produced discrepant results. [10][11][12] The immunologic effects of high-dose compared to lowdose vitamin D in patients with MS remain unclear. We also sought to confirm that cholecalciferol at 10,000 IU daily is well-tolerated in patients with MS.

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“…There were no significant differences in EDSS scores between MS patients treated with IFNβ and those not treated (data not shown). As this treatment may alter vitamin D status (Stewart et al, 2012), 1,25(OH) 2 D, 25(OH)D, and DBP levels were compared between these treatment groups. Patients treated with IFNβ had significantly higher serum levels of 1,25(OH) 2 D compared with those not treated with IFNβ ( Fig.…”

Section: Serum Levels Of 125(oh) 2 D 25(oh)d and Dbp In Subjects Imentioning

confidence: 99%

Decreased serum vitamin D levels in Japanese patients with multiple sclerosis

Niino

Sato

Fukazawa

et al. 2015

Journal of Neuroimmunology

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Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS

Abstract: This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.

Cited by 89 publications

References 26 publications

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

Decreased serum vitamin D levels in Japanese patients with multiple sclerosis

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