Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene.
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the -174 G/C and -572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the -174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the -174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the -174 G/C polymorphism.
Trevelyan
Jasper
J
Department of Cardiology, University Hospitals of Coventry and Warwickshire, Coventry, United Kingdom. dr.trevelyan@virgin.net
Brull
David J
DJ
Needham
Edward W A
EW
Montgomery
Hugh E
HE
Morris
Alan
A
Mattu
Raj K
RK
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D004656:Enalapril / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000959:Antihypertensive Agents; D016207:Cytokines; D015850:Interleukin-6; D004656:Enalapril; D019808:Losartan