Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis

被引:64
作者
Kimball, Samantha [1 ,2 ]
Vieth, Reinhold [1 ,2 ,3 ]
Dosch, Hans-Michael [4 ]
Bar-Or, Amit [5 ,6 ]
Cheung, Roy [4 ]
Gagne, Donald [5 ]
O'Connor, Paul [7 ,8 ]
D'Souza, Cheryl [9 ]
Ursell, Melanie [10 ]
Burton, Jodie M. [7 ,8 ]
机构
[1] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Nutr Sci, Toronto, ON M5G 1X5, Canada
[3] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5G 1X5, Canada
[4] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada
[5] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
[6] McGill Univ, Expt Therapeut Program, Montreal, PQ H3A 2B4, Canada
[7] Univ Toronto, St Michaels Hosp, Div Neurol, Toronto, ON M5B 1W8, Canada
[8] Univ Toronto, Dept Neurol, Toronto, ON M5B 1W8, Canada
[9] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M58 3H2, Canada
[10] Oshawa Clin, Oshawa, ON L1H 1B9, Canada
基金
美国国家卫生研究院; 加拿大健康研究院;
关键词
VITAMIN-D SUPPLEMENTATION; RESONANCE-IMAGING LESIONS; CENTRAL-NERVOUS-SYSTEM; T-CELLS; 1,25-DIHYDROXYVITAMIN D-3; RELAPSE RATE; SEASONAL FLUCTUATIONS; 25-HYDROXYVITAMIN D; PATIENTS TARGET; D DEFICIENCY;
D O I
10.1210/jc.2011-0325
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: The active metabolite of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], is a potent modulator of immune cells in vitro. Objective: Our objective was to determine whether the sun-dependent nutrient, cholecalciferol, can alter disease-associated cellular immune abnormalities in patients with multiple sclerosis (MS). Design: This was an open-label, 12-month, randomized controlled trial. Setting: Patients with MS were recruited from the MS Clinic at St. Michael's Hospital, Toronto. Patients: Forty-nine patients were matched(for age, sex, disease duration, disease-modifying drug, and disability) and enrolled (treated n = 25; control n = 24). Four patients were lost to follow-up (n = 2 from each group). Intervention: Treated patients received increasing doses of cholecalciferol (4,000-40,000 IU/d) plus calcium (1200 mg/d), followed by equilibration to a moderate, physiological intake (10,000 IU/d). Control patients did not receive supplements. Main Outcome Measures: At enrollment and at 12 months, peripheral blood mononuclear cell (PBMC) proliferative responses to disease-associated, MS-relevant, and control antigens were measured, along with selected serum biochemical markers. Results: At 12 months, mean serum 25-hydroxyvitamin D [25(OH)D] concentrations were 83 +/- 35 nmol/liter and 179 +/- 76 nmol/liter in control and treated participants, respectively (paired t, P < 0.001). Serum 1,25(OH)(2)D did not differ between baseline and 1 yr. In treated patients, 12-month PBMC proliferative responses to neuron antigens myelin basic protein and exon-2 were suppressed (P = 0.002). In controls, there were no significant changes in disease-associated PBMC responsiveness. There were no significant differences between groups in levels of selected biomarkers. Interpretation: MS-associated, abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH) D concentrations higher than 100 nmol/liter. (J Clin Endocrinol Metab 96: 2826-2834, 2011)
引用
收藏
页码:2826 / 2834
页数:9
相关论文
共 48 条
[1]  
Auer DP, 2000, ANN NEUROL, V47, P276, DOI 10.1002/1531-8249(200002)47:2<276::AID-ANA28>3.0.CO
[2]  
2-1
[3]   Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes [J].
Banwell, Brenda ;
Bar-Or, Amit ;
Cheung, Roy ;
Kennedy, Julia ;
Krupp, Lauren B. ;
Becker, Dorothy J. ;
Dosch, Hans-Michael .
ANNALS OF NEUROLOGY, 2008, 63 (01) :98-111
[4]   A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis [J].
Burton, J. M. ;
Kimball, S. ;
Vieth, R. ;
Bar-Or, A. ;
Dosch, H. -M. ;
Cheung, R. ;
Gagne, D. ;
D'Souza, C. ;
Ursell, M. ;
O'Connor, P. .
NEUROLOGY, 2010, 74 (23) :1852-1859
[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]   The role of antigen presenting cells in multiple sclerosis [J].
Chastain, Emily M. L. ;
Duncan, D'Anne S. ;
Rodgers, Jane M. ;
Miller, Stephen D. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2011, 1812 (02) :265-274
[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]   Immunomodulatory effects of Vitamin D in multiple sclerosis [J].
Correale, Jorge ;
Celica Ysrraelit, Mara ;
Ines Gaitan, Maria .
BRAIN, 2009, 132 :1146-1160
[9]   Human kallikrein 6 as a biomarker of Alzheimer's disease [J].
Diamandis, EP ;
Yousef, GM ;
Petraki, C ;
Soosaipillai, AR .
CLINICAL BIOCHEMISTRY, 2000, 33 (08) :663-667
[10]  
Embry AF, 2000, ANN NEUROL, V48, P271, DOI 10.1002/1531-8249(200008)48:2<271::AID-ANA28>3.0.CO