Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

Kamal Ivory, Elena Prieto, Caroline Spinks, Charlotte N Armah, Andrew J Goldson, Jack R Dainty, Claudio Nicoletti, Kamal Ivory, Elena Prieto, Caroline Spinks, Charlotte N Armah, Andrew J Goldson, Jack R Dainty, Claudio Nicoletti

Abstract

Background & aims: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50-64 years.

Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 μg Se/day (SeY-0/d; n = 20), 50 μg Se/d (SeY-50/d; n = 18), 100 μg Se/d (SeY-100/d; n = 21) or 200 μg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 μg Se/d (SeO-0/d; n = 17) or 50 μg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12.

Results: Primary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY-200/d). SeO (Se 50 μg/d) also enhanced T cell proliferation after vaccination (650%), IFN-γ (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-α synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation.

Conclusion: Se-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation.

Keywords: Cellular immunity; Food supplements; Humoral immunity; Influenza; Selenium.

Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Patient recruitment and retention is described (M, Male; F, Female).
Fig. 2
Fig. 2
Proliferating T cells in isolated mononuclear cells cultured for 5 days with flu antigens. Weeks 0 and 10 samples were respectively collected before Se supplementation or flu vaccination. Panel A shows group specific differences throughout the study period. Panel B shows the same data as Se dose-associated trends by linear or polynomial fit. Values are means ± SEMs; *different from relevant control group (P n = 10; SeY-50/d, n = 9; SeY-100/d, n = 28; SeY-200/d, n = 15; SeO-0/d, n = 12; SeO-50/d, n = 14. SeO, selenium onion; SeY, selenium yeast.
Fig. 3
Fig. 3
Effect of Se supplementation on (A) NKT and (B) Tctx-ADCC cell counts/μL blood. Weeks 0 and 10 samples were respectively collected before Se supplementation or flu vaccination. Values are means ± SEMs; *different from relevant control group (P n = 20; SeY-50/d, n = 20; SeY-100/d, n = 21; SeY-200/d, n = 23; SeO-0/d, n = 17; SeO-50/d, n = 18. NKT, natural killer T.; Tctx-ADCC, T cells that mediate antibody-dependent cell cytotoxicity, SeO, selenium onion; SeY, selenium yeast.
Fig. 4
Fig. 4
Granzyme B+ (A) and perforin+ (B) CD8 subsets within isolated mononuclear cells cultured for 3 days with flu antigens. Weeks 0 and 10 samples were respectively collected before Se supplementation or flu vaccination. Values are means ± SEMs; *different from relevant control group (P < 0.05). SeY-0/d, n = 15; SeY-50/d, n = 12; SeY-100/d, n = 16; SeY-200/d, n = 19. SeO-0/d, n = 12, SeO-50/d, n = 16. SeO, selenium onion, SeY, selenium yeast.
Fig. 5
Fig. 5
Secreted protein concentrations in supernatants from isolated mononuclear cells cultured for 5 days with or without flu antigens. Weeks 0 and 10 samples were respectively collected before Se supplementation or flu vaccination. In order to account for different baseline (week 0) values these have been subtracted from subsequent time points. Values are means ± SEMs; *different from relevant control group (P n = 17; SeY-50/d, n = 15; SeY-100/d, n = 18; SeY-200/d, n = 19; SeO-0/d, n = 13; SeO-50/d, n = 16. SeO, selenium onion; SeY, selenium yeast.
Fig. 6
Fig. 6
Titers of flu-specific serum IgG1 (A,D), serum IgG3 (B) and fold change in salivary IgA (C). Weeks 0 and 10, samples were respectively taken before Se supplementation or flu vaccination. 1, week 0; 2, week 10; 3, week 11; 4, week 12. Values are means ± SEMs for serum IgG (A,B); *different from relevant control group (P n = 17; SeY-50/d, n = 16; SeY-100/d, n = 19; SeY-200/d, n = 21; SeO-0/d, n = 15; SeO-50/d, n = 17. SeO, selenium onion; SeY, selenium yeast.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5381341/bin/figs1.jpg

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