Abstract
Vitamins C and D are known to have immunomodulatory effects. Current recommendations state that plasma 25-hydroxyvitamin D3 should be maintained above 50 nmol/L, although concentrations of 100 nmol/L can enhance health benefits. Concentrations below 25 and 12.5 nmol/L are considered insufficient and deficient, respectively. The typical plasma ascorbate concentration is 50 μmol/L. Vitamin C supplementation can increase plasma concentration to 100–150 μmol/L. Vitamin C insufficiency and deficiency occur at 25 μmol/L and <10 μmol/L, respectively. This study investigates cytokine production by THP-1 monocytes and macrophages, following vitamin C and D treatment at concentrations representing deficiency, insufficiency, sufficiency and following supplementation. Macrophages were differentiated from THP-1 monocytes using PMA. THP-1 cells (monocytes or macrophages) were pre-treated with ascorbate or 25-hydroxyvitamin D3 for 24 h at the aforementioned concentrations, then challenged with lipopolysaccharide for 6 and 24 h. Extracellular concentrations of IL-1β, IL-6, IL-10 and TNF-α were measured using Luminex assays. In THP-1 monocytes, 25-hydroxvitamin D3 and ascorbate, at concentrations representing sufficiency and supplementation, decreased TNF-α, IL-1β and IL-6 at 6 and 24 h. Ascorbate at concentrations of >50 μmol/L also increased IL-10 at both time points. At supplemented concentrations, 25-hydroxvitamin D3 and ascorbate lowered the TNF-α/IL-10 ratio from 39:1 to 31:1 and 17:1, respectively, at 6 h. At 24 h, TNF-α/IL-10 was lowered from 88:1 to 31:1, following 150 μmol/L ascorbate treatment, and from 185:1 to 108:1 following 100 nmol/L 25-hydroxyvitamin D3 treatment. In THP-1 macrophages, pro-inflammatory cytokines were unaffected by 25-hydroxvitamin D3 at 6 h. However, IL-10 concentration increased at concentrations > 50 nmol/L. At 24 h, the inflammatory cytokines decreased as the 25-hydroxyvitamin D3 concentration increased. 25-hydroxvitamin D3 (100 nmol/L) reduced the TNF-α/IL-10 ratio from 88:1 to 64:1 at 6 h and from 105:1 to 35:1 at 24 h. Ascorbate, at concentrations representing sufficiency and supplementation, decreased the inflammatory cytokines at 6 and 24 h. Ascorbate at 150 μmol/L decreased TNF-α/IL-10 from 116:1 to 35:1 at 6 h and from 102:1 to 21:1 at 24 h. These data demonstrate that both 25-hydroxyvitamin D3 and ascorbate decrease the inflammatory burden in THP-1 monocytes and THP-1 derived macrophages. Future work will investigate vitamin interactions and underlying mechanisms.
Author Contributions
Conceptualization, M.D. and P.C.; methodology, M.D.; formal analysis, M.D.; investigation, M.D.; writing—original draft preparation, M.D.; writing—review and editing, C.C., E.M. and P.C.; supervision, C.C., E.M. and P.C.; project administration, P.C.; funding acquisition, P.C. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Bayer Consumer Care AG.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data is available from the corresponding author upon request.
Conflicts of Interest
P.C. is an ad hoc advisor to Bayer Consumer Care, Haleon Consumer Healthcare and dsm-fermenich. M.D., C.C. and E.M. declare no conflicts of interrest.
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