Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia.
OBJECTIVE
The purpose of this study was to assess if simvastatin has an anti-inflammatory activity in patients with hypercholesterolemia.


BACKGROUND
Simvastatin, an inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, reduced cardiovascular events in patients with myocardial infarction and hypercholesterolemia.


METHODS
Sixteen patients with polygenic hypercholesterolemia were randomly allocated to diet (n = 8) or diet plus 20 mg/day simvastatin (n = 8) for eight weeks. Before and at the end of treatment period, lipid profile and monocyte expression of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) were measured.


RESULTS
At baseline no difference in lipid profile and monocyte expression of TNF and IL-1beta were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1beta was seen. In patients with diet plus simvastatin, significant decreases of total cholesterol (-27%, p<0.02), low density lipoprotein-cholesterol (-33%, p<0.02), and monocyte expression of TNF (-49%, p<0.02) and IL-1beta (-35%, p<0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1beta than did patients assigned to diet alone.


CONCLUSIONS
This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1beta expressed by monocytes.
Istituto I Clinica Medica, Università La Sapienza, Rome, Italy.
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Ferro
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Parrotto
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Basili
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Alessandri
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Violi
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin