ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 16 of 50
JMBS 2018, 3(7): 96–101
Clinical Medicine

Dynamics of Immune System Parameters in Elderly Patients on the Background of Vitamin D3 Intake

Grishyna O. I., Babinets O. M., Menkus O. V.

The aim: Research of dynamics of the levels of lymphocytes with determinants of CD3, CD3CD4, CD3CD8, CD19, CD3CD56NK, IFN-γ, IL-4, IL-19, IL-23, immunoglobulin (Ig) classes of A, M, G, total complement (CH50), circulating immune complexes (CIC) under the influence of long-term use of vitamin D3 in the elderly. Forty patients aged 65 to 79 years old, with vitamin D3 deficiency, were randomized in the 2 groups. Twenty one patients in the group “1” took vitamin D3 over 2 months by 4,000 IU per day. Nineteen patients in the group "2" did not take cholecalciferol. Groups were comparable by gender and age, p ≥ 0.05. Patients had polymorbid pathology, the first three places in which were given to arterial hypertension, coronary heart disease, osteoarthritis. The average number of diseases per 1 patient in the group "1" was (M ± SD) (6.3 ± 2.1) versus (6.2 ± 1.9) in the group "2", p ≥ 0.05. The study did not include patients with autoimmune diseases. Determination of the number of lymphocytes in the peripheral blood with antigenic CD determinants was performed using kits manufactured by BD Multitest, USA. Levels of cytokines, CH50, CIC, 25-OH Vitamin D were determined by kits manufactured by DRG International, Inc., USA. Content of serum Ig classes A, M, G, using ready-made sets of reagents "Ig A, M, G – IFA" ("Granum", Ukraine). The research was carried out in compliance with the basic bioethical provisions of the Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (of 04.04.1997), the Helsinki Declaration of the World Medical Association – Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects (1964-2008), as well as the order Ministry of Health of Ukraine No. 690 dated September 23, 2009. Indicators of humoral immunity were initially comparable in groups "1" and "2". The intake of vitamin D3 was accompanied by an increase in the content of the total complement of CH50: (70,5 ± 15,7) g/l vs (75,8 ± 17,4) g/l and Ig M (1,04 ± 0,3) g/l vs (1,84 ± 0,6) g/l and a decrease in the values Ig G (11,0 ± 3,2) g/l vs (9,9 ± 3,2) g/l and the CIC (12,2 ± 3,5) vs (10,1 ± 3,3), p < 0,05 in all cases. The level of Ig A has not changed. In group "2" none of the indicators significantly changed. Accordingly, differences in the levels of CH50 and Ig M were formed after 2 months between the groups that were significantly higher in the group "1" and the content Ig G - significantly less in the group "1". There were no discrepancies in the levels of CIC and Ig A. The baseline levels of cell-mediated immunity between groups "1" and "2" did not differ significantly. The content of CD3 and CD3CD4 in patients in the group "1" was raised in response to the use of vitamin D3 compared with baseline: (852,15 ± 278,26)% versus (1104,28 ± 317,97)% and (410,23 ± 127.85)% versus (782.51 ± 264.15)%, respectively, p <0.05 in all cases. The values of CD3CD8 decreased: (493.19 ± 158.64)% versus (383.16 ± 131.27)%, CD19: (133.41 ± 43.3)% versus (101.98 ± 32.5)%, and CD3CD56NK (62.2 ± 21.3)% vs. (48.4 ± 16.4)%, respectively, p <0.05 in all cases. Similar dynamics in group "2" were not observed. Accordingly, when comparing the studied parameters in 2 months, patients who received vitamin D3 had higher CD3 and CD3CD4, and lower CD3CD8, CD19. The CD3CD56NK level did not differ between groups after 2 months. Patients in both groups were comparable output levels of IL-23, IL-4, IL-19 and IFN-γ. Patients in group "1" after the course of vitamin D3 intake had a decrease in IL-23 levels: (9.3 ± 3.1) pg/ml versus (7.2 ± 2.4) pg/ml, p <0.05. The IFN-γ concentration did not differ significantly before and after the course of treatment. The opposite results were obtained for IL-4 and IL-19: (17.8 ± 6.2) pg/ml against (25.5 ± 7.1) pg/ml and (35.5 ± 11.7) pg/ml (48.7 ± 13.4) pg/ml, respectively, after the course of vitamin therapy among patients in group "1" levels of these cytokines significantly increased. The following analysis data in group "2" did not differ from the output. Our data indicate that patients receiving vitamin D3 had higher rates of total complement CH50 and Ig M, lower Ig G and CIC values after 2 months of admission compared to non-vitamin D3 patients. Thus, taking vitamin D3 provides beneficial immunological effects in inclined patients associated with normalization of indices of humoral immunity. It also provides a reduction in the number of B cells, effector T cells and an increase in regulatory T cells, a decrease in the level of proinflammatory cytokine IL-23, and an increase in levels of anti-inflammatory cytokines IL-4 and IL-19. In this case, the IFN-γ content required to maintain the anti-infective response is not reduced.

Keywords: elderly, vitamin D3, T-lymphocytes, immunoglobulins, circulating immune complexes, cytokines

Full text: PDF (Ukr) 206K

  1. Holick MF. Vitamin D Deficiency. N Engl J Med. 2007; 357(3): 266-81.
  2. Takeuchi A, Reddy GS, Kobayashi T, Okano T, Park J, Sharma S. Nuclear factor of activated T cells (NFAT) as a molecular target for 1alpha,25-dihydroxyvitamin D3-mediated effects. J Immunol. 1998; 160(1): 209-18.
  3. Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009; 4(9): 1151-65.
  4. Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004; 89-90(1-5): 575-9.
  5. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, Landry ML Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS ONE. 2010; 5: e11088.
  6. Tavera-Mendoza LE, White JH. Cell defenses and the sunshine vitamin. Sci Am. 2007; 297(5): 62-72.
  7. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum. 2007; 66 (9): 1137–42.
  8. Ginde AA, Scragg R, Schwartz RS, Camargo CA. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older US adults. J Am Geriatr Soc. 2009; 57(9): 1595-603.
  9. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008; 168(12): 1340-9.
  10. Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CD, Snijder MB, et al. Vitamin D and mortality in older men and women. Clin Endocrinol (Oxf). 2009; 71(5): 666-72.
  11. Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr. 2013; 97(4): 782-93.
  12. Consolini R, Pala S, Legitimo A, Crimaldi G, Ferrari S, Ferrari S. Effects of vitamin D on the growth of normal and malignant B cell progenitors. Clin Exp Biol. 2001; 126(2): 214–9.
  13. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human cell differentiation. J Immunol. 2007; 179(3): 1634–47.
  14. Lemire J, Adams JS, Sakai R, Jordan SC. M. 1-α, 25-hydroxyvitamin D3 suppresses proliferation and immunoglobulin production by human blood mononuclear cells. J Clin Invest. 1984; 74(2): 657–61.
  15. Müller K, Bendtzen K. Inhibition of human T-lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3. Differential effects on CD45RA+ and CD45R0+ cells. Autoimmunity. 1992; 14(1): 37–43.
  16. Müller K, Bendtzen K. 1,25-dihydroxyvitamin D3 as a natural regulator of human immune functions. J Investig Dermatol Symp Proc. 1996; 1(1): 68–71.
  17. Provvedini DM, Tsoukas CD, Leftos LJ, et al. 1α, 25-dihydroxyvitamin D3 binding macromolecules in human B lymphocytes: effects on immunoglobulin production. J Immunol. 1986; 136(8): 2734–40.
  18. Savustyanenko AV. Vlyyanye vytamynov na funktsyyu ymmunnoy systemy, detoksykatsyyu y dlytelnost zhyzny. Novosty medytsyny y farmatsyy. 2010; 21(349).
  19. Alkhedaide AQH, Alshehri ZS, Soliman MM, Althumali KhW, Abu-Elzahab HS, Baiomy AAA. Vitamin D3 supplementation improves immune and inflammatory response in vitamin D deficient adults in Taif, Saudi Arabia. Biomedical Research. 2016; 27(4): 1049–53.