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Treatment with atorvastatin alters interleukin‐12 and ‐10 gene expression
Author(s) -
Naoumova R. P.,
Patel D. D.,
O'Neill F. H.,
Thompson G. R.,
Knight B. L.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01105.x
Subject(s) - atorvastatin , mevalonic acid , hydroxymethylglutaryl coa reductase , cholesterol , endocrinology , medicine , placebo , peripheral blood mononuclear cell , messenger rna , hmg coa reductase , interleukin , pharmacology , interleukin 6 , chemistry , cytokine , enzyme , in vitro , biochemistry , biosynthesis , reductase , gene , alternative medicine , pathology
Abstract Background Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol. Material and methods Seventeen patients with heterozygous familial hypercholesterolaemia participated in a single‐blind placebo controlled study. The patients underwent three treatment regimens: placebo (4 weeks), atorvastatin 10 mg day −1 (4 weeks) and atorvastatin 40 mg day −1 (12 weeks). Following each treatment period, serum lipids and plasma mevalonic acid were measured, mononuclear leukocytes were isolated and total RNA was prepared. The content of mRNA for IL‐12p35 and IL‐10 was assayed, blinded, by real‐time quantitative polymerase chain reactions. Results Treatment of the subjects with atorvastatin decreased the abundance of IL‐12p35 mRNA in mononuclear cells, but did not alter that of IL‐10, so that the ratio of the IL‐12p35 to IL‐10 mRNA content was significantly reduced ( P < 0·0026). The IL‐12p35/IL‐10 ratio correlated significantly with plasma mevalonic acid concentrations but not with serum LDL concentrations. Conclusions This study provides evidence that atorvastatin exerts an immunomodulatory effect in vivo , characterized by a decrease in the ratio of IL‐12 mRNA to IL‐10 mRNA in leukocytes. The immunomodulatory effect of statins, in addition to their cholesterol‐lowering properties, may contribute to the rapid cardiovascular benefit observed during treatment with statins and reduced the rate of rejection in patients with solid organ transplantation.