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Treatment with atorvastatin alters the ratio of interleukin-12/interleukin-10 gene expression [corrected]
R P Naoumova1, D D Patel, F H O'Neill
1MRC Clinical Sciences Center, Collier Building, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. rossi.naoumova@csc.mrc.ac.uk
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.
Insights
Atorvastatin reduces the ratio of IL-12p35 to IL-10 mRNA in leukocytes, indicating an immunomodulatory effect beyond cholesterol-lowering. This finding may explain statins' rapid cardiovascular benefits and reduced transplant rejection rates.
Area of Science:
- Immunology
- Pharmacology
- Genetics
Background:
- Statins possess pleiotropic effects beyond cholesterol reduction.
- Investigating the immunomodulatory impact of statins is crucial for understanding their broader therapeutic applications.
Purpose of the Study:
- To investigate the immunomodulatory effects of atorvastatin in patients with heterozygous familial hypercholesterolaemia.
- To determine the impact of atorvastatin on the mRNA expression of IL-12p35 and IL-10 in leukocytes.
Main Methods:
- A single-blind, placebo-controlled study involving 17 patients with heterozygous familial hypercholesterolaemia.
- Patients received placebo, atorvastatin 10 mg, and atorvastatin 40 mg for distinct periods.
- Real-time quantitative polymerase chain reaction was used to measure mRNA levels of IL-12p35 and IL-10 in isolated mononuclear leukocytes.
Main Results:
- Atorvastatin treatment significantly decreased the abundance of IL-12p35 mRNA, while IL-10 mRNA levels remained unchanged.
- The ratio of IL-12p35 to IL-10 mRNA was significantly reduced following atorvastatin administration (P < 0.0026).
- The IL-12p35/IL-10 ratio correlated with plasma mevalonic acid but not with serum LDL concentrations.
Conclusions:
- Atorvastatin demonstrates an in vivo immunomodulatory effect by decreasing the IL-12 mRNA to IL-10 mRNA ratio in leukocytes.
- This immunomodulatory action, alongside lipid-lowering effects, may contribute to the rapid cardiovascular benefits of statins.
- Statins' immunomodulatory properties might also play a role in reducing rejection rates in solid organ transplant recipients.
