Abstract

  Multiple sclerosis (MS) is a chronic autoimmune disease of central nervous system which etiology remains unclear. Worldwide studies suggest strong link between vitamin D deficiency and MS. In this study, we conducted a systematic literature search regarding the effect of high dose vitamin D treatment in immunological parameters of MS patients. High dose vitamin D treatment promotes few significant chances in immunological systemic markers, mainly in the total amount of peripheral blood IL-17+CD4+ T cells and in the proportion of TH IL-4+ cells. In summary, high dose treatment promotes limited differences in immunological markers in patients with MS.

Keywords: Multiple Sclerosis; Vitamin D; Treatment; Systematic Review; Supplementation

References

1. Kimball S., et al. “Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis”. The Journal of Clinical Endocrinology and Metabolism9 (2011): 2826-2834.
2. Polman CH., et al. “Diagnostic Criteria for Multiple Sclerosis: 2010 Revisions to the McDonald Criteria”. Annals of Neurology2 (2011): 292-302.
3. Zurawski J and Stankiewicz J. “Multiple Sclerosis Re-Examined: Essential and Emerging Clinical Concepts”. The American Journal of Medicine5 (2018): 464-472.
4. Dörr J., et al. “Can We Prevent or Treat Multiple Sclerosis by Individualised Vitamin D Supply?” EPMA Journal 1 (2013): 4.
5. Ascherio A and Munger KL. “Environmental Risk Factors for Multiple Sclerosis. Part II: Noninfectious Factors”. Annals of Neurology6 (2007): 504-513.
6. Casaccia-Bonnefil P., et al. “Evaluating Epigenetic Landmarks in the Brain of Multiple Sclerosis Patients: A Contribution to the Current Debate on Disease Pathogenesis”. Progress in Neurobiology4 (2008): 368-378.
7. Burrell AM., et al. “Epigenetic Mechanisms in Multiple Sclerosis and the Major Histocompatibility Complex (MHC)”. Discovery Medicine58 (2011): 187-196.
8. Pakpoor J and Ramagopalan S. “Evidence for an Association Between Vitamin D and Multiple Sclerosis”. (2014): 105-115.
9. Simon KC., et al. “Vitamin D and Multiple Sclerosis”. Current Opinion in Neurology3 (2012): 246-251.
10. Smolders J., et al. “Vitamin D as an Immune Modulator in Multiple Sclerosis, a Review”. Journal of Neuroimmunology1-2 (2008): 7-17.
11. D’Ambrosio, D., et al. “Inhibition of IL-12 Production by 1,25-Dihydroxyvitamin D3. Involvement of NF-KappaB Downregulation in Transcriptional Repression of the P40 Gene”. Journal of Clinical Investigation 1 (1998): 252-262.
12. Adorini L., et al. “Dendritic Cells as Key Targets for Immunomodulation by Vitamin D Receptor Ligands”. The Journal of Steroid Biochemistry and Molecular Biology 89-90 (2004): 437-441.
13. Joshi S., et al. “1,25-Dihydroxyvitamin D3 Ameliorates Th17 Autoimmunity via Transcriptional Modulation of Interleukin-17A”. Molecular and Cellular Biology17 (2011): 3653-3669.
14. Gatenby P., et al. “Vitamin D Deficiency and Risk for Rheumatic Diseases”. Current Opinion in Rheumatology 2 (2013): 184-191.
15. Shoemaker TJ and Mowry EM. “A Review of Vitamin D Supplementation as Disease-Modifying Therapy”. Multiple Sclerosis Journal1 (2018): 6-11.
16. Chang J., et al. “1,25-Dihydroxyvitamin D3 Inhibits the Differentiation and Migration of TH17 Cells to Protect against Experimental Autoimmune Encephalomyelitis”. PLoS ONE9 (2010): e12925.
17. Chiuso-Minicucci F., et al. “Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis”. PLOS ONE5 (2015): e0125836.
18. Ashtari F., et al. “Short-Term Effect of High-Dose Vitamin D on the Level of Interleukin 10 in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial”. Neuroimmunomodulation6 (2015): 400-404.
19. Darwish H., et al. “Effect of Vitamin D Replacement on Cognition in Multiple Sclerosis Patients”. Scientific Reports1 (2017): 45926.
20. Berger VW and Alperson SY. “A General Framework for the Evaluation of Clinical Trial Quality”. Reviews on Recent Clinical Trials2 (2009): 79-88.
21. Åivo J., et al. “Vitamin D3 Administration to MS Patients Leads to Increased Serum Levels of Latency Activated Peptide (LAP) of TGF-Beta”. Journal of Neuroimmunology 280 (2015): 12-15.
22. Shirvani-Farsani Z., et al. “Vitamin D Levels in Multiple Sclerosis Patients: Association with TGF-Β2, TGF-ΒRI, and TGF-ΒRII Expression”. Life Sciences 134 (2015): 63-67.
23. Gargari BN., et al. “Vitamin D Supplementation Up-Regulates IL-6 and IL-17A Gene Expression in Multiple Sclerosis Patients”. International Immunopharmacology1 (2015): 414-419.
24. Golan D., et al. “Vitamin D Supplementation for Patients with Multiple Sclerosis Treated with Interferon-Beta: A Randomized Controlled Trial Assessing the Effect on Flu-like Symptoms and Immunomodulatory Properties”. BMC Neurology1 (2013): 60.
25. Muris A., et al. “Immune Regulatory Effects of High Dose Vitamin D3 Supplementation in a Randomized Controlled Trial in Relapsing Remitting Multiple Sclerosis Patients Receiving IFNβ; the SOLARIUM Study”. Journal of Neuroimmunology 300 (2016): 47-56.
26. Rolf L., et al. “Correlation of Different Cellular Assays to Analyze T Cell-Related Cytokine Profiles in Vitamin D3-Supplemented Patients with Multiple Sclerosis”. Molecular Immunology 105 (2019): 198-204.
27. Rolf L., et al. “Vitamin D 3 Supplementation and the IL-2/IL-2R Pathway in Multiple Sclerosis: Attenuation of Progressive Disturbances?” Journal of Neuroimmunology 314 (2018): 50-57.
28. Røsjø E., et al. “Vitamin D Supplementation and Systemic Inflammation in Relapsing-Remitting Multiple Sclerosis”. Journal of Neurology 12 (2015): 2713-2721.
29. Sotirchos ES., et al. “Safety and Immunologic Effects of High- vs Low-Dose Cholecalciferol in Multiple Sclerosis”. Neurology 4 (2016): 382-390.
30. Toghianifar N., et al. “Effect of High Dose Vitamin D Intake on Interleukin-17 Levels in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial”. Journal of Neuroimmunology 285 (2015): 125-128.
31. Fitzgerald KC., et al. “Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b”. JAMA Neurology12 (2015): 1458.
32. Zheng C., et al. “The Efficacy of Vitamin D in Multiple Sclerosis: A Meta-Analysis”. Multiple Sclerosis and Related Disorders 23 (2018): 56-61.
33. Alhassan Mohammed H., et al. “Immunomodulatory and Immunosuppressive Roles of 1α,25 (OH)2D3 in Autoimmune Diseases”. Scandinavian Journal of Immunology 2 (2017): 95-103.
34. Sintzel MB., et al. “Vitamin D and Multiple Sclerosis: A Comprehensive Review”. Neurology and Therapy1 (2018): 59-85.
35. Huang W., et al. “Multiple Sclerosis: Pathology, Diagnosis and Treatments”. Experimental and Therapeutic Medicine6 (2017): 3163-3166.
36. Lassmann H. “Multiple Sclerosis Pathology”. Cold Spring Harbor Perspectives in Medicine3 (2018): a028936.
37. Danikowski KM., et al. “Regulatory T Cells in Multiple Sclerosis and Myasthenia Gravis”. Journal of Neuroinflammation 1 (2017): 117.
38. Li Y., et al. “Levels of Peripheral Th17 Cells and Serum Th17-Related Cytokines in Patients with Multiple Sclerosis: A Meta-Analysis”. Multiple Sclerosis and Related Disorders 18 (2017): 20-25.
39. Zimmermann J., et al. “IL-17A Promotes Granulocyte Infiltration, Myelin Loss, Microglia Activation, and Behavioral Deficits During Cuprizone-Induced Demyelination”. Molecular Neurobiology2 (2018): 946-957.
40. Wojkowska D., et al. “Interleukin 17A Promotes Lymphocytes Adhesion and Induces CCL2 and CXCL1 Release from Brain Endothelial Cells”. International Journal of Molecular Sciences5 (2017): 1000.
41. Annunziato, F., et al. “Defining the Human T Helper 17 Cell Phenotype”. Trends in Immunology 10 (2012): 505-512.
42. Bhargava P., et al. “1,25-Dihydroxyvitamin D3 Impairs the Differentiation of Effector Memory T Cells in Vitro in Multiple Sclerosis Patients and Healthy Controls”. Journal of Neuroimmunology 279 (2015): 20-24.
43. Bose T. “Role of Immunological Memory Cells as a Therapeutic Target in Multiple Sclerosis”. Brain Sciences12 (2017): 148.
44. Kaneko A., et al. “1,25-Dihydroxyvitamin D3 Suppresses the Expression of the VCAM-1 Receptor, VLA-4 in Human Leukemic HL-60 Cells”. Biochemical and Biophysical Research Communications2 (1999): 371-376.
45. Stüve O and Bennett J L. “Pharmacological Properties, Toxicology and Scientific Rationale for the Use of Natalizumab (Tysabri®) in Inflammatory Diseases”. CNS Drug Reviews1 (2007): 79-95.
46. Stelmasiak Z., et al. “Interleukin-6 Concentration in Serum and Cerebrospinal Fluid in Multiple Sclerosis Patients”. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research6: 1104-1108.
47. Holmøy T., et al. “Inflammation Markers in Multiple Sclerosis: CXCL16 Reflects and May Also Predict Disease Activity”. PLoS ONE, edited by Pablo Villoslada 9 (2013): e75021.
48. Smolders J., et al. “An Update on Vitamin D and Disease Activity in Multiple Sclerosis”. CNS Drugs 12 (2019): 1187-1199.
49. Hupperts R., et al. “Randomized Trial of Daily High-Dose Vitamin D 3 in Patients with RRMS Receiving Subcutaneous Interferon β-1a”. Neurology (2019): 10.1212/WNL.0000000000008445.
50. Camu W., et al. “Cholecalciferol in Relapsing-Remitting MS: A Randomized Clinical Trial (CHOLINE)”. Neurology - Neuroimmunology Neuroinflammation5 (2019): e597.
51. Langer-Gould A., et al. “Vitamin D-Binding Protein Polymorphisms, 25-Hydroxyvitamin D, Sunshine and Multiple Sclerosis”. Nutrients 2 (2018): 184.
52. Langer-Gould A., et al. “MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics”. Nutrients 3 (2018): 268.

Citation

Citation: Rômulo Tadeu Dias de Oliveira., et al. “Influence of High Doses Vitamin D Therapy at Immunological Parameters in Multiple Sclerosis Patients. A Systematic Review". Acta Scientific Medical Sciences 3.10 (2020): 164-175.

Copyright

Copyright: © 2020 Rômulo Tadeu Dias de Oliveira., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.