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

被引:108
作者
Sotirchos, Elias S. [1 ]
Bhargava, Pavan [1 ]
Eckstein, Christopher [2 ]
Van Haren, Keith [3 ]
Baynes, Moira [1 ]
Ntranos, Achilles [1 ]
Gocke, Anne [1 ]
Steinman, Lawrence [3 ]
Mowry, Ellen M. [1 ]
Calabresi, Peter A. [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[2] Duke Univ, Sch Med, Dept Neurol, Durham, NC USA
[3] Stanford Univ, Sch Med, Dept Neurol, Palo Alto, CA 94304 USA
关键词
VITAMIN-D SUPPLEMENTATION; T-CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; CONTROLLED-TRIAL; 25-HYDROXYVITAMIN D; MONONUCLEAR-CELLS; RELAPSE RISK; DOUBLE-BLIND; EXPRESSION; MULTICENTER;
D O I
10.1212/WNL.0000000000002316
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 relapsing-remitting 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 low-dose 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-17(+)CD4(+) T cells (p = 0.016), CD161(+)CD4(+) T cells (p = 0.03), and effector memory CD4(+) T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4(+) T cells (p = 0.018) and naive CD4(+) T cells (p = 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 CD4(+) T cells and decreased proportion of effector memory CD4(+) T cells with concomitant increase in central memory CD4(+) T cells and naive CD4(+) 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.
引用
收藏
页码:382 / 390
页数:9
相关论文
共 37 条
[1]   Coordinated expression of ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells [J].
Anfossi, N ;
Doisne, JM ;
Peyrat, MA ;
Ugolini, S ;
Bonnaud, O ;
Bossy, D ;
Pitard, V ;
Merville, P ;
Moreau, JF ;
Delfraissy, JF ;
Dechanet-Merville, J ;
Bonneville, M ;
Venet, A ;
Vivier, E .
JOURNAL OF IMMUNOLOGY, 2004, 173 (12) :7223-7229
[2]   1,25-Dihydroxyvitamin D3 impairs the differentiation of effector memory T cells in vitro in multiple sclerosis patients and healthy controls [J].
Bhargava, Pavan ;
Gocke, Anne ;
Calabresi, Peter A. .
JOURNAL OF NEUROIMMUNOLOGY, 2015, 279 :20-24
[3]   The Vitamin D to Ameliorate Multiple Sclerosis (VIDAMS) trial: Study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis [J].
Bhargava, Pavan ;
Cassard, Sandra ;
Steele, Sonya U. ;
Azevedo, Christina ;
Pelletier, Daniel ;
Sugar, Elizabeth A. ;
Waubant, Emmanuelle ;
Mowry, Ellen M. .
CONTEMPORARY CLINICAL TRIALS, 2014, 39 (02) :288-293
[4]   Chemokine receptor expression on MBP-reactive T cells:: CXCR6 is a marker of IFN-γ-producing effector cells [J].
Calabresi, PA ;
Yun, SH ;
Allie, R ;
Whartenby, KA .
JOURNAL OF NEUROIMMUNOLOGY, 2002, 127 (1-2) :96-105
[5]   1,25-dihydroxyvitamin D-3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis [J].
Cantorna, MT ;
Hayes, CE ;
DeLuca, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7861-7864
[6]   A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells [J].
Colonna, M ;
Navarro, F ;
Bellon, T ;
Llano, M ;
Garcia, P ;
Samaridis, J ;
Angman, L ;
Cella, M ;
LopezBotet, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (11) :1809-1818
[7]   Gender Differences in 1,25 Dihydroxyvitamin D3 Immunomodulatory Effects in Multiple Sclerosis Patients and Healthy Subjects [J].
Correale, Jorge ;
Ysrraelit, Maria C. ;
Gaitan, Maria I. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (08) :4948-4958
[8]   Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor [J].
Cosmi, Lorenzo ;
De Palma, Raffaele ;
Santarlasci, Veronica ;
Maggi, Laura ;
Capone, Manuela ;
Frosali, Francesca ;
Rodolico, Gabriella ;
Querci, Valentina ;
Abbate, Gianfranco ;
Angeli, Roberta ;
Berrino, Liberato ;
Fambrini, Massimiliano ;
Caproni, Marzia ;
Tonelli, Francesco ;
Lazzeri, Elena ;
Parronchi, Paola ;
Liotta, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio ;
Annunziato, Francesco .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (08) :1903-1916
[9]   Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial [J].
Doerr, Jan ;
Ohlraun, Stephanie ;
Skarabis, Horst ;
Paul, Friedemann .
TRIALS, 2012, 13
[10]   1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization [J].
Grishkan, Inna V. ;
Fairchild, Amanda N. ;
Calabresi, Peter A. ;
Gocke, Anne R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (52) :21101-21106