title: Effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases in hypercholesterolemic individuals.
abstract: Statins are potent lipid-lowering drugs but anti-inflammatory effects have also been suggested. Our aim was to investigate the effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases (MMPs). Eighty hypercholesterolemic men were randomized to simvastatin 40 mg or placebo for 6 weeks. Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged. The ex vivo release of IL-1β and IL-6 was not altered by simvastatin, whereas the release of TNF-α and IL-8 increased after 6 weeks of simvastatin treatment. Similarly, the circulating levels of MMP-3 and TIMP-1 remained unaffected by simvastatin while MMP-9 increased. However, none of the effects except for the CRP reduction within the simvastatin group reached statistical significance when compared to the placebo group. Our findings are in contrast to previous in vitro and animal data and question the in vivo relevance of some of the pleiotropic effects of simvastatin.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 58185, Linköping, Sweden. lennart.nilsson@liu.se
authors.forename: Lennart
authors.initials: L
authors.lastname: Nilsson
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Pierre
authors.initials: P
authors.lastname: Cherfan
authors.forename: Lena
authors.initials: L
authors.lastname: Jonasson
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002097:C-Reactive Protein / Q000096:biosynthesis*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D019715:Tissue Inhibitor of Metalloproteinase-1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D020782:Matrix Metalloproteinases