Effects of simvastatin on human T cells in vivo.
OBJECTIVE
The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo.


RESULTS
A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h)1/Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-gamma and interleukin-4. Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2.


CONCLUSIONS
Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia.
Cherfan
Pierre
P
Department of Internal Medicine, Högland Hospital, Eksjö, Sweden.
Tompa
Andrea
A
Wikby
Anders
A
Löfgren
Sture
S
Jonasson
Lena
L
D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D004311:Double-Blind Method; D004768:Enterotoxins / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D019041:L-Selectin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D001053:Apolipoproteins; D004768:Enterotoxins; D006684:HLA-DR Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053645:Interleukin-2 Receptor alpha Subunit; D008055:Lipids; D003208:Concanavalin A; D019041:L-Selectin; C031818:enterotoxin B, staphylococcal; D002097:C-Reactive Protein; D019821:Simvastatin