Table 2.
The immunomodulatory roles of minerals reported by experimental studies.
| Minerals | Dose/Concentration | Study Model | Findings | References |
|---|---|---|---|---|
| Zinc | 91 mg/kg | In vivo (mice) | Increases Treg cells, decreases severity of EAE, and decreases Th17 RORγT+ cells | [224] |
| 6.77 μM | Pro-inflammatory TNF-α and IL-6 | Causes zinc depletion, decreases production of TNF-α and IL-6, and increases phagocytosis and oxidative burst | [225] | |
| 10 mg/day for 10 days | In vitro (PBMCs) | Decreases Th1-cytokine production and proliferation in MLC, prolongs Foxp3 expression, causes Sirt-1 inhibition and induces regulatory T cells in MLC | [226] | |
| 10 μM, 20 μM, or 45 μM zinc sulfate/pyrithione (50 μM) | In vitro (PBMCs) | Suppresses activation of IκB kinase β (IKKβ) and NF-κB TNF-α release and subsequent TNF-α production. Contributes to anti-inflammatory action of PDE inhibitors | [227] | |
| 2 mM Zn2+ and 2 mM PT | In vitro (Vero-E6 cells) | Inhibits the RNA-synthesizing activity of the RTCs and blocks the initiation step of EAV RNA synthesis | [228] | |
| 1 μM + 10 μM pyrithione | In vitro (PBMCs) | Reduces mRNA expression of proinflammatory cytokines, and inhibits LPS-mediated toxicity | [229] | |
| zinc-deficient diet (0.5–1.5 ppm zinc) or a matched control diet (50.5–51.5 ppm zinc) | In vivo (mice) | Zinc-deficient dietary intake causes excessive inflammation to polymicrobial sepsis in conjunction, ZIP8 is a potent negative regulator of NF-kB activation | [230] | |
| Iron | 10, 50 or 100 μM | In vivo (mice) | Dietary iron loading lowers inflammatory responses such as Il-1β expression, decreases M1 marker, CD86, and I-A/I-E expression, increases IL-4, ↓NF- κB p65 nuclear translocation, and decreases iNos and pro-inflammatory cytokines expression | [231] |
| 250 μM | In vivo (diabetic mice) | Dietary iron overload causes hepatic oxidative stress and NLRP3 inflammasome activation, increase in hepatic inflammatory mediators and immune cell activation, upregulation of chemokine, cytokine, and antioxidant mediators such as iNos, TNF-α, Mcp1, hepcidin (gene name Hamp), Hmox1, and Tlr4 | [232] | |
| (0.2–10 mg iron/kg; 0.2 mL/mouse) | In vivo (mice) | Decreases CD3+ and F4/80+ cells, decreases DTH reactions, and IFN-γ production, increases IL-4 production, and decreases splenic CD11b+ cells | [233] | |
| ferumoxytol (2.73 mg Fe mL−1, 8.37 mg Fe mL−1 | In vivo (mice model) | Inhibits growth of subcutaneous adenocarcinomas Increases the presence of pro-inflammatory M1 macrophages in the tumor tissues |
[234] | |
| ferumoxytol (0–30 mg mL−1) | In vitro (mammary tumor cells) | Iincreases caspase-3 activity, increases mRNA associated with pro-inflammatory Th1-type responses, Increases production of tumor-necrosis factor-α (TNF-α) |
[234] | |
| FAC (0∼400 μg/mL) | In vitro (RAW264.7 macro-phage cell line) | Decreases mRNA levels of IL-6, IL-1, TNF-α, and decreases iNOS production | [235] | |
| Selenium | 0.08 to 1.00 mg/kg | In vivo (mice) | Increases CD4+ T cell responses and differentiation, increases Ca2+ mobilization, oxidative burst, and NFAT translocation, increases IL-2 transcription, IL-2 receptor expression, and proliferation | [236] |
| with or without 0.2 ppm Se | In vivo (mice) | Mice fed a Se-deficient diet have more adult worms than Se-sufficient diet. Se-sufficient diet increased Il4, Il13, and Il13ra2 expression and decreased Il4 and Il13 expression. Restores anti-fecundity response | [237] | |
| 100 nmol/L Se | In vitro (BMDM culture) | Increases Arg-I, Fizz1, and Mrc-1 expression, decreases TNF-α and IL-1β expression, produces endogenous activators to mediate the PPARg-dependent switch from M1 to M2 phenotype and participate in wound healing and inflammation | [238] | |
| MSA (2.41 μg/mL, 1.5 μg/mL Se) and MSC (4.15 μg/mL, 1.5 μg/mL Se) | In vitro (S. aureus Culture) | Displays a greater defense against uterine inflammatory damage, decreases necrosis factor alpha (TNF-α) and increases interleukin-6 (IL-6), ↓phosphorylation of IκBα and ↓NF-κB p65 | [239] | |
| MSA (0 to 30 μM) | In vitro (DLBCL cell lines) | Inhibits HDAC activity, acetylation of histone H3 | [240] | |
| 0.03 to 1.5 mg/kg | In vivo (mice) | Se-deficient mice increase TNF-α, IL-1β, and IL-6 production, increase mRNA and protein expressions of toll-like receptor 2 (TLR2) | [241] | |
| 100 μg/day | In vivo (mice) | Increases IFN-γ and IL-12 production, higher survival rate, and DTH response | [242] | |
| 0.1 ppm | In vivo (mice) | ↑interferon-γ, ↑interleukin IL-6 | [243] | |
| 100 μg/kg | In vivo (mice) | ↑CD4+ CD25+ Foxp3+ T cells, ↑Foxp3 mRNA expression | [244] | |
| 200 μg of Se | In vitro (PBMCs) | ↑Interleukin (IL-2, IL-4, IL-5, IL-13, and IL-22) | [245] | |
| Magnesium | 60 mg/Lor 2.5 mM | In vitro (PBMCs) | ↓production of TNF-α and IL-6 in maternal and neonatal, ↓cytokine production, ↓NF-kB activation, ↑constitutive IkBa level | [219] |
| 5 nM to 20 nM | In vivo (murine) | Inhibits activation of macrophage, ↓percentage of CCR7-positive cells, ↓cytokines (IL-1β, IL-6 and IL-10), ↓nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB), ↑chondrogenic differentiation of hBMSCs | [246] | |
| Mg2+ (0, 1, 3 and 5 mM) | In vitro (murine MSCs cells) | ↑proliferation rates of MSCs, ↓IL-1β and IL-6, ↑IL-10 and PGE2, ↓pNF-κB/NF-κB, ↑pSTAT-3/STAT-3, modulating the production of IL-1β and IL-6 | [218] | |
| concentrations of Mg- supplemented (0.8, 5, 10, 15, and 20 mmol/L) | In vitro (asthmatic CD4+T cells) | ↓IL-5 and IL-13 secretion, ↑IFN-y secretion, modulating the immune responses of acute asthmatic CD4* T cells | [247] | |
| 499 mg/kg and 44 mg/kg in the control diet and the low-Mg diet, respectively | In vivo (rat) | Mg deficiency increased the levels of mRNA known to be expressed by mast cells in the liver; mast cells were locally distributed around portal triads | [248] | |
| 32 and 950 mg/kg respectively for deficient and control diets | In vivo (rats) | In Mg deficient diet ↑interleukin-6 (IL-6) level, higher u2-macroglobulin and u1-acid glycoprotein, ↑plasma fibrinogen and ↓ albumin concentration | [249] | |
| Copper | 1 µm Cu group, 200 mg/kg CuCl2 group, 200 mg/kg nano-Cu low group, 50 mg/kg nano-Cu medium group, 100 mg/kg nano-Cu nano-Cu high group, 200 mg/kg |
In vivo (rat) | Decreased antibody production (IgA, IgG, IgM) altered lymphocyte subpopulation in the spleen, altered the number of blood cells, induces oxidative stress | [250] |
| 20–1000 mg/kg DW nCu- treated seeds (nCu-1000); 2–1000 mg nCu/l-treated mice |
In vivo (mice) | Administration of mice with 1000 mg/l nCu leading to inflammatory responses, upregulated expression of serum biochemical indicators of liver and kidney, increased infiltration and activation of splenic immune cells | [251] | |
| 163 mM/L copper sulfate | In vitro (stromal cell) | Copper disrupted the endometrial receptivity signature of dHESCs, decreases IGFBP1 levels, does not increase the apoptosis level | [252] | |
| 163 mM/L copper sulfate | In vitro (endometrial cells) | Changes in the gene expression (42 up- and 9 downregulated), does not increase the apoptosis level induced by the decidualization treatment | [252] |