Table I.

Evidence on immunomodulatory effect of statins in humans and mice

Statin	Dose	Experimental model	Possible mechanism	Ref.
Simvastatin	In vitro: 2 µM	Mice, Treg/Th17 differentiation	↑ Differentiation of CD4 into Treg ↓ Differentiation of Th17 ↑ SOCS3	[105]
Simvastatin	In vitro: 5 µM	Human	↑ IL-4, IL-5, IL-13 ↓ INF-γ ↓ T-bet expression ↑ GATA 3 and B220 expression	[106]
Simvastatin	In vitro: 10 nM	Human, PBMCs from MS patients and healthy controls	↓ IL-6 and IL-23 ↑ INF-γ, IL-4, and Il-27 ↓ RORC and IL17 gene expression ↑ SOCS3	[107]
Simvastatin	10, 50 mg/kg	Mice, tumor growth of 3LL cell line	↑ Fox-p3, IDO, IL-10, and TGF-β	[108]
Simvastatin	In vitro: 10 mM	Human, PBMC from SCA patients	↑ Treg cells’ number ↑ Treg cells’ suppressive activity	[109]
Simvastatin	In vitro: 10 mM	Human , monocytes	↑ SOCS 3 and 7 ↑ INF-γ, IL-4 and IL-27 ↓ JAK-STAT expression ↓ IL-6, IL-23 and IL-17	Reference
Simvastatin	In vitro: 10 µM	Human, mDC from asthmatic patients	↓ Th17 cells, ↓ IL-6, ↓ IL-23 ↑ Treg cells ↑ IDO and ↑ IL-10	[110]
Simvastatin	In vitro: 0.5–2 µM	Mice, Treg differentiation	↑ Differentiation of Treg ↑ Foxp3 expression ↓ SMAD6 and SMAD7 ↓ Methylation of foxp3 promoter	[111]
Fluvastatin, lovastatin, and simvastatin,	In vitro: all at 10 µM	Mice, T cell	↑ Kruppel-like factor 2 (KLF2) expression ↓ INF-γ ↓ Differentiation of T-cells	[49]
Rosuvastatin	5 mg/kg i.v.	Mice, Ischemia-reperfusion injury	↑ Foxp3 expression	[112]
Fluvastatin	0.1, 1.0, or 10 µM	Human, PBMCs from 7 patients with asthma	↓ IL-5, IFN-γ, CCL17, and CXCL10 Prevention of Th1 and Th2 cell migration	[113]
Lovastatin	10 mg/kg i.p.	Mice, DTH (C. albicans)	↑ Migration of Tregs to the foot-pad ↑ CCl1 and IL-10	[114]
Lovastatin	6.25, 12.5, 25 µM	Human	↑ Bak expression (apoptosis regulators) ↓ Bcl-XL expression activation of caspase-3/8/9 ↓ Collagen and platelet aggregation	[115]
Lovastatin	0.5–25 mM	Human, PBMC from patients with CIU	↓ T-cell proliferation ↓ IL-10 and IL-17 ↔ Neither Socs3 nor RORc	[116]
Atorvastatin	10 mg/kg	Mice, experimental autoimmune glomerulonephritis	↑ IL-10, ↓ IL-17, IFN-γ ↓ TNF-γ IL-21 Treg	[117]
Atorvastatin	20 mg/kg	Human, twenty-seven healthy volunteers	↓ HLA-DR and CD38 expression ↑ Superantigen-mediated T cell activation
Atorvastatin	In vitro: 10 mM	Human endothelial cell culture	↓ Expression of CD40	[64]
Atorvastatin	10 mg/kg/day	Mice with EAE, control mice	↑ Th2 cytokine secretion ↓ Th1 cytokine secretion	[118]
Atorvastatin	In vitro: 10 mM	Mice, experimental autoimmune myasthenia gravis	↑ Foxp3 expression, ↑ Treg number ↓ Lymphocyte proliferation ↓ Th1/Th17, ↑ Th2	[67]
Atorvastatin	In vitro: 5–10 mM	Human, PBMC culture	↑ Treg cells’ number ↑ Suppressive function of Tregs	[119]