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. 2020 Jun 1;17:19. doi: 10.1186/s12989-020-00349-z

Table 4.

In vivo studies on immunological properties of NPs

NPs Time Cell response Cell frequency/activity Dose range Potential effect Ref
TiO2 1 -14 d ↗ IFN-ɣ and IL-17 in spleen ↗ Th17 and Th1 in spleen 10 mg/kg bw/d inflammation [116]
↗ DC frequency in PP imbalance immune response
↙ Treg and T helper cells in PP immunossuppression

↗ inflammatory cytokines in ileum

(IL-12, IL-4, IL-23, TNF-α, IFN-γ)

↗ T cells CD4+ in small intestin 100 mg/kg bw/d inflammation [161]
5 g/kg bw (single oral gavage) no toxic effects [165]
> 28 d ↗ TNF-α, IL-10 and IL-8 in colon ↙ Treg and T helper cells in PP 10 mg/kg bw/d risk of preneoplasic lesions in colon [116]

↗ IL-6, TNF-α, IL1-β in ovary

(expression and production)

↙ white cells and lymphocytes in blood 2.5; 5; 10 mg/kg bw/d inflammation and follicule atresia [166]
fertility reduction
↗ glucose in blood of young rats ↗ mast cells activation in stomach 10, 50, 200 mg/kg bw/d alteration of gastrointestinal functions [167]
Heart, Liver and Kidney injuries
SiO2 7 -14 d

↙ inflammatory cytokines in blood

(IL1-β, TNF-α, IL-12p70, IL-6 and IFN-ɣ)

↙ Natural Killer acitivity in spleen 750 mg/kg bw/d immunossuppression [168]
↙ T cells and B cells proliferation in spleen dysregulation of immune response
↙ Lymphocytes population in blood
↗ IgG and IgE in blood ↗ splenocyte proliferation 0.1; 1; 10 mg/mouse/d imbalance immune response (dose dependent) [162]

↗ inflammatory cytokines in spleen

(INF-ɣ, IL-4, IL-5 and IL-17)

risk of food allergy development
≥ 28 d slight ↗ lymphocytes in blood 2.5 mg/mouse/d no effect [169]
Ag 7-14 d ↗ TGF-β in blood

↗ B and Natural Killer cells in blood

↗ T CD8+ population in blood

1 mg/kg bw/d imbalance immune response [170]

↗ IgG in blood,

↗ TGF-β and IFN-ɣ in spleen

↗ splenocyte proliferation 0.01; 0.1; 1; 10 mg/kg bw/d imbalance immune response [163]
≥ 28 d

↗ inflammatory cytokines in blood

(IL1-β, IL-6, IL-4, IL-10, IL-12 and TGF-β)

↗ T CD8+ population in blood 0.25; 0.50; 1 mg/kg bw/d inflammation [170]
↗ IgE in blood ↗ B cell in blood risk of food allergy development

↙ gene expression in ileum

(MUC3, TLR2, TLR4, FOXP3, IL-10, TGF-β)

9 mg/kg bw/d immunossuppression [105]
sexual dimorphism response

The relevant doses for humans are indicated in bold. DC dendritic cell, FOXP3 forkhead box P3, GPR43 G-protein coupled receptor 43, IFN-γ interferon-gamma, Ig immunoglobulin, IL interleukin, MUC3 mucin 3, NOD2 nucleotide-binding oligomerization domain 2, TGF-β transforming growth factor beta, Th T helper, TLR Toll-like receptor, TNF-α tumor necrosis factor alpha, Treg regulatory T-cell