Статья
Рассеянный склероз и уровень обеспеченности витамином D
Хорошо известно, что рассеянный склероз (РС) является хроническим иммуноопосредованным заболеванием центральной нервной системы, характеризующимся поражением преимущественно белого вещества головного и спинного мозга, проявляющимся хроническим прогрессирующим течением и приводящим к необратимой инвалидизации людей молодого возраста, что определяет его высокую социальную и экономическую значимость. Результаты проведенных исследований свидетельствуют о мультифакторной природе этого заболевания. Полагают, что одним из факторов риска развития РС может быть низкий уровень обеспеченности витамином D. Исследование «неклассических» эффектов витамина D, в том числе его влияния на иммунную систему, получило широкое развитие в последние годы. Обзор посвящен анализу клинических и экспериментальных данных об ассоциации дефицита витамина D и рассеянного склероза, обсуждению патогенетических аспектов влияния витамина D на течение этого заболевания, а также анализу необходимости и способов коррекции дефицита витамина D при РС. В публикации представлены данные о перспективах проведения дальнейших исследований в этой области с целью установления оптимальных доз, режима и продолжительности лечения препаратами витамина D при РС.
1. Шмидт Т. Е., Яхно Н. Н. Рассеянный склероз: руководство для врачей. 2-е изд.М.: МЕДпресс-информ; 2010. 272 с..
2. Гусев Е. И., Бойко А. Н., Столяров И. Д. (ред.). Рассеянный склероз: справочник. СПб: ЭЛБИ-М; 2009. C. 29–33..
3. Скоромец А. А., Тотолян Н. А., Барбас И. М. Рассеянный склероз: критерии диагноза и современная терапия. Новые Санкт-Петербургские врачебные ведомости. 2005;3:66–76..
4. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol. 2010;6(3):156–66. doi: 10.1038/nrneurol.2010.1.
5. Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599–612. doi: 10.1016/S1474– 4422 (10)70086–7.
6. Kurtzke JF. MS epidemiology worldwide. One view of current status. Acta Neurol Scand Suppl. 1995;161:23–33.
7. Acheson ED, Bachrach CA, Wright FM. Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation, and other variables. Acta Psychiatr Scand Suppl. 1960;35(147):132–47.
8. Haussler MR, Haussler CA, Jurutka PW, Thompson PD, Hsieh JC, Remus LS et al. The vitamin D hormone and its nuclear receptor: molecular actions and disease states. J Endocrinol. 1997;154 Suppl: S57–73.
9. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357 (3):266–81.
10. Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int. 2009;20(1):133–40. doi: 10.1007/s00198–008– 0626-y.
11. Pierrot-Deseilligny C, Souberbielle JC. Widespread vita min D insufficiency: a new challenge for primary prevention with particular reference to multiple sclerosis. Presse Med. 2011;40 (4 Pt 1):349–56. doi: 10.1016/j.lpm.2011.01.003.
12. Каронова Т. Л., Гринёва Е. Н., Никитина И. Л., Цветкова Е. В., Тодиева А. М., Беляева О. Д. и соавт. Распространенность дефицита витамина D в Северо-Западном регионе РФ среди жителей г. Санкт-Петербурга и г. Петрозаводска. Остеопороз и остеопатии. 2013;3:3–7..
13. Munger KL, Ascherio A. Risk factors in the development of multiple sclerosis. Expert Rev Clin Immunol. 2007;3(5):739–48. doi: 10.1586/1744666X.3.5.739.
14. Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010;133(Pt 7):1869–88. doi: 10.1093/brain/awq147.
15. Hanwell HE, Banwell B. Assessment of evidence for a protective role of vitamin D in multiple sclerosis. Biochim Biophys Acta. 2011;1812(2):202–12. doi: 10.1016/j.bbadis.2010.07.017.
16. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010;10 (4):482–96. doi: 10.1016/j.coph.2010.04.001.
17. Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC. Canadian Collaborative Study Group. Timing of birth and risk of multiple sclerosis: population based study. Br Med J. 2005;330(7483):120.
18. Ascherio A, Munger KL, White R, Kochert K, Simon KC, Polman CH et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014;71(3):306–14. doi: 10.1001/jamaneurol.2013.5993.
19. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Am Med Assoc. 2006;296(23):2832–8.
20. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT. Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol. 2003;134 (1–2):128–32.
21. Correale J, Ysrraelit MC, Gaitan MI. Vitamin D-mediated immune regulation in multiple sclerosis. J Neurol Sci. 2011;311 (1–2):23–31. doi: 10.1016/j.jns.2011.06.027.
22. Royal W, Mia Y, Li H, Naunton K. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol. 2009;213 (1–2):135–41. doi: 10.1016/j.jneuroim.2009.05.012.
23. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, Stelmasiak Z, Rolinski J. Immunomodulatory effects of vitamin D on monocytederived dendritic cells in multiple sclerosis. Mult Scler. 2010;16 (12):1513–6. doi: 10.1177/1352458510379611.
24. Lysandropoulos AP, Jaquiéry E, Jilek S, Pantaleo G, Schluep M, Du Pasquier RA. Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects. J Neuroimmunol. 2011;233(1–2):240–4. doi: 10.1016/j.jneuroim.2010.11.008.
25. Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009;256(9):1468– 79. doi: 10.1007/s00415–009–5139-x.
26. Becklund BR, Hansen DW Jr, Deluca HF. Enhancement of 1,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis by calcitonin. Proc Natl Acad Sci USA. 2009;106(13):5276–81. doi: 10.1073/pnas.0813312106.
27. Branisteanu DD, Waer M, Sobis H, Marcelis S, Vandeputte M, Bouillon R. Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 alpha, 25(OH)2D3. J Neuroimmunol. 1995;61(2):151–60.
28. Cantorna MT, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D3 reversibly blocks the progression of encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA. 1996;93(15):7861–4.
29. Lemire JM, Archer DC. 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. 1991;87(3):1103–7.
30. Nashold FE, Miller DJ, Hayes DE. 1,25-dihydroxyvitamin D3 treatment decreases macrophage accumulation of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol. 2000;103(2):171–9.
31. Nashold FE, Hoag KA, Goverman J, Hayes CE. Rag-1dependent cells are necessary for 1,25-dihydroxyvitamin D3 prevention of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2001;119(1):16–29.
32. Nataf S, Garcion E, Darcy F, Chabannes D, Muller JY, Brachet P. 1,25-dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1996;55(8):904–14.
33. Pedersen LB, Nashold FE, Spach KM, Hayes CE. 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokines synthesis and monocyte trafficking. J Neurosci Res. 2007;85(11):2480–90.
34. Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol. 2005;175(6):4119–26.
35. Spach KM, Nashold FE, Dittel BN, Hayes CE. IL-10 signaling is essential for 1,25-dihydroxyvitamin d3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol. 2006;177(9):6030–7.
36. Tjellesen L, Christiansen C, Hummer L, Larsen NE. Unchanged biochemical indices of bone turnover despite fluctuations in 1,25-dihydroxyvitamin D during the menstrual cycle. Acta Endocrinol (Copenh). 1983;102(3):476–80.
37. van Hoof HJ, van der Mooren MJ, Swinkels LM, Sweep CG, Merkus JM, Benraad TJ. Female sex hormone therapy increases serum free 1,25-dihydroxyvitamin D3: a 1-year prospective study. Clin Endocrinol (Oxf). 1999;50(4):511–6.
38. Spach KM, Pedersen LB, Nashold FE, Kayo T, Yandell BS, Prolla TA et al. Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics. 2004;18(2):141–51.
39. Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol. 1998;160(11):5314–9.
40. Chaudhuri A. Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis. Med Hypotheses. 2005;64(3):608–18.
41. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). 2004;229(11):1136–42.
42. Muthian G, Raikwar HP, Rajasingh J, Bright JJ. 1,25-dihydroxyvitamin D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic encephalomyelitis. J Neurosci Res. 2006;83(7):1299–309.
43. Mattner F, Smiroldo S, Galbiati F, Muller M, Di Lucia P, Poliani PL et al. Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3. Eur J Immunol. 2000;30(2):498–508.
44. Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 2005;289(1): F8–28.
45. Cantorna MT, Humpal-Winter J, DeLuca HF. Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. J Nutr. 1999;129(11):1966–71.
46. Fernandes de Abreu DA, Ibrahim EC, Boucraut J, Khrestchatisky M, Féron F. Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers. J Steroid Biochem Mol Biol. 2010;121 (1–2):250–3. doi: 10.1016/j.jsbmb.2010.03.006.
47. DeLuca HF, Plum LA. Vitamin D deficiency diminishes the severity and delays onset of experimental autoimmune encephalomyelitis. Arch Biochem Biophys. 2011;513(2):140–3. doi: 10.1016/j.abb.2011.07.005.
48. Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006;371(1–2): 1–12.
49. Tizaoui K, Kaabachi W, Hamzaoui A, Hamzaoui K. Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies. Cell Mol Immunol. 2015;12 (2):243–52. doi: 10.1038/cmi.2014.47.
50. Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflamm atory diseases. Front Physiol.2014;5:244. doi: 10.3389/fphys.2014. 00244.
51. Huang J, Xie ZF. Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk: A meta-analysis of case-control studies. J Neurol Sci. 2012;313(1–2):79–85. doi: 10.1016/j. jns.2011.09.024.
52. Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses. 1986;21 (2):193–200.
53. Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005;76(9):1294–6.
54. Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74(23):1852–9. doi: 10.1212/WNL.0b013e3181e1cec2.
55. Smolders J, Peelen E, Thewissen M, Cohen Tervaert JW, Menheere P, Hupperts R et al. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One. 2010;5(12): e15235. doi: 10.1371/journal.pone.0015235.
56. Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611–8. doi: 10.1212/WNL.0b013e3182343274.
57. Soilu-Hänninen M, Aivo J, Lindstrom BM, Elovaara I, Sumelahti ML, Farkkila M et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(5):565–71. doi: 10.1136/jnnp-2011–301876.
58. Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler. 2012;18(8):1144–51. doi: 10.1177/1352458511434607.
59. Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H. Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int. 2012;2012:452–541. doi: 10.1155/2012/452541.
60. James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013;19 (12):1571–9. doi: 10.1177/1352458513489756.
61. Brum DG, Comini-Frota ER, Vasconcelos CC, DiasTosta E. Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology. Arq Neuropsiquiatr. 2014;72(2):152–6. doi: 10.1590/0004– 282X20130252.
62. Hughes S. Vitamin D for all to prevent MS? 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Medscape; October 03, 2013. Available from: http://www.medscape. com/viewarticle/812045#vp_1