Statins as Modulators of Regulatory T-Cell Biology

Table 2

Evidences on the modulation of Treg cells by statins in humans.

Statin	Dose	Subjects and approach	Possible mechanism involving Treg	Ref.
Atorvastatin	20 mg/day for 1 month	Two groups: 25 stable renal transplant recipients with LDL > 100 and 25 hypercholesterolemic patients with LDL level above target values. Measures were done before and after treatment	↓ Lymphocyte proliferation; ↑ ATP in CD4^+ T cells; ↔ Cytokines	[33]
Atorvastatin	In vitro: 10 mM	Human endothelial cell culture	↓ Expression of CD40	[38]
Atorvastatin	In vitro: 5–10 mM	PBMC culture	↑ Treg cells number; ↑ Suppressive function of Tregs	[32]
Atorvastatin	In vitro: 10 mM; In vivo: 20 mg/d	PBMC from patients with RA	↑ Treg cells number; ↑ Treg cells suppressive function; ↓ Phosphorylation of Akt, mTOR, and ERK	[47]
Atorvastatin	80 mg	Blood samples obtained from the ICA and a peripheral vein, STEMI patients	↑ Number of CD4^+ CD25^+ Tregs; ↓ INF-γ; ↑ Expression of Foxp3; ↑ TGF-β	[29]
Simvastatin/lovastatin	0.5–25 mM	PBMC from patients with CIU	↓ T-cell proliferation; ↓ IL-10 and Il17; ↔ Neither Socs3 nor RORc	[24]
Simvastatin	In vitro: 10 nM	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	[45]
Simvastatin	In vitro: 10 mM	PBMC from SCA patients	↑ Treg cells number; ↑ Treg cells suppressive activity	[28]
Simvastatin	In vitro: 10 mM	Naive CD4^+ T cells derived from MS patients	↓ Th17 differentiation; ↓ IL-17A, IL-17F, and IL-21; ↓ IRF4 phosphorylation; ↓ Rho/ROCK kinase activity	[46]
Simvastatin	In vitro: 10 µM	mDC from asthmatic patients	↓ Th17 cells, ↓ IL-6, ↓ IL-23; ↑ Treg cells ↑ IDO and ↑ IL-10	[48]