Treatment with atorvastatin alters the ratio of interleukin-12/interleukin-10 gene expression [corrected].
BACKGROUND
Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol.


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.
Naoumova
R P
RP
MRC Clinical Sciences Center, Collier Building, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. rossi.naoumova@csc.mrc.ac.uk
Patel
D D
DD
O'Neill
F H
FH
Thompson
G R
GR
Knight
B L
BL
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D053765:Interleukin-12 Subunit p35; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008055:Lipids / Q000097:blood; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D008875:Middle Aged; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016037:Single-Blind Method
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D008055:Lipids; D021122:Protein Subunits; D011758:Pyrroles; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D000069059:Atorvastatin; D008798:Mevalonic Acid