Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are 
in widespread use due to their LDL reducing properties and concomitant 
improvement of clinical outcome in patients with and without preexisting 
atherosclerosis. Considerable evidence suggests that immune mediated mechanisms 
play a dominant role in the beneficial effects of statins. Naturally occurring 
CD4(+)CD25(+) regulatory T cells (Tregs) have a key role in the prevention of 
various inflammatory and autoimmune disorders by suppressing immune responses. 
We tested the hypothesis that statins influence the circulating number and the 
functional properties of Tregs. We studied the effects of in vivo and in vitro 
statin treatment of human and murine mononuclear cells on the number of Tregs 
and the expression level of their master transcription regulator, Foxp3. 
Atorvastatin, but not mevastatin nor pravastatin, treatment of human peripheral 
blood mononuclear cells (PBMCs) increased the number of CD4(+)CD25(high) cells, 
and CD4(+)CD25(+)Foxp3(+) cells. These Tregs, induced by atorvastatin, expressed 
high levels of Foxp3, which correlated with an increased regulatory potential. 
Furthermore, co-culture studies revealed that atorvastatin induced 
CD4(+)CD25(+)Foxp3(+) Tregs were derived from peripheral CD4(+)CD25(-)Foxp3(-) 
cells. Simvastatin and pravastatin treatment in hyperlipidemic subjects 
increased the number of Tregs. In C57BL/6 mice however, no effect of statins on 
Tregs was evident. In conclusion, statins appear to significantly influence the 
peripheral pool of Tregs in humans. This finding may shed light on the 
mechanisms governing the plaque stabilizing properties of statins.