Statins as Modulators of Regulatory T-Cell Biology

Table 1

Lines of evidence on the modulation of regulatory T cells by statins in mice.

Statin	Dose	Experimental model	Possible mechanism involving Treg	Ref.
Atorvastatin	1–10 mg/kg	Experimental autoimmune neuritis	↑ Treg number; ↓ Inflammatory cells; ↓ INF-𝛾^+ and IL-17^+ cells; ↓ CD80 expression	[44]
Atorvastatin	10 mg/kg	Experimental autoimmune glomerulonephritis	↑ IL-10, ↓ IL-17, IFN-g ↓ TNF-γ ↓ IL-21; ↕ Treg	[50]
Atorvastatin	In vitro: 10 mM	Experimental autoimmune myasthenia gravis	↑ Foxp3 expression, ↑ Treg number; ↓ Lymphocyte proliferation ↓ Th1/Th17, ↑ Th2	[25]
Lovastatin	10 mg/kg i.p	DTH (C. albicans)	↑ Migration of Tregs to the foot-pad; ↑ CCl1 and IL-10	[36]
Rosuvastatin	5 mg/kg i.v.	Ischemia-reperfusion injury	↑ Foxp3 expression	[30]
Simvastatin	10, 50 mg/kg	Tumor growth of 3LL cell line	↑ Fox-p3, IDO, IL-10, and TGF-β	[53]
Simvastatin	In vitro: 0.5–2 µM	Treg differentiation	↑ Differentiation of Treg; ↑ Foxp3 expression; ↓ SMAD6 and SMAD7; ↓ Methylation of foxp3 promoter	[34]
Simvastatin	In vitro: 2 µM	Treg/Th17 differentiation.	↑ Differentiation of CD4 into Treg; ↓ Differentiation of Th17; ↑ SOCS3	[43]
Simvastatin	20 mg/kg	Toxoplasma gondii small intestine inflammation	↓ INF-γ, TNF-α, IL-23, and IL-6; ↑ Foxp3^+ cells; ↑ IL-10; ↓ Neutrophils, and MCP-1	[49]
Simvastatin	50/mg/kg	ApoE−/− mice model of atherosclerosis	↑ Treg cells number; ↑ Foxp3 expression; ↓ IL-1β, IL-17, and INF-γ; ↑ TGF-B, IL-10, and IL4	[28]