CLINICAL STUDIES
Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia
Domenico Ferro, MD*,
Sandro Parrotto, MD*,
Stefania Basili, MD ,
Cesare Alessandri, MD and
Francesco Violi, MD*
* Istituto I Clinica Medica, Università "La Sapienza," Rome, Italy
Dipartimento di Terapia Medica, Università "La Sapienza," Rome, Italy
Istituto di Terapia Medica Sistematica, Università "La Sapienza," Rome, Italy
Manuscript received October 4, 1999;
revised manuscript received February 16, 2000,
accepted April 5, 2000.
Reprint requests and correspondence to: Prof. Francesco Violi, MD, I Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00185 Rome, Italy
violi{at}uniroma1.it
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- (TNF) and interleukin-1ß (IL-1ß) were measured.
RESULTS
At baseline no difference in lipid profile and monocyte expression of TNF and IL-1ß were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1ß 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-1ß (–35%, p < 0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1ß than did patients assigned to diet alone.
CONCLUSION
This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1ß expressed by monocytes.
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Abbreviations and Acronyms
| | HDL-C | = high density lipoprotein cholesterol | | HMG-CoA | = 3-hydroxy-methyl-glutaryl coenzyme A | | IL-1ß | = interleukin 1-beta | | LDL-C | = low density lipoprotein cholesterol | | TC | = total cholesterol | | TNF | = tumor necrosis factor-alpha |
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