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

• Published in: The American journal of cardiology 2004-09, Vol.94 (5), p.564-569
• Main Authors: Trevelyan, Jasper, Brull, David J., Needham, Edward W.A., Montgomery, Hugh E., Morris, Alan, Mattu, Raj K.
• Format: Article
• Language: English
• Subjects: Aged; Angina pectoris; Angina Pectoris - drug therapy; Angina Pectoris - genetics; Angina Pectoris - immunology; Angina Pectoris - surgery; Antihypertensive Agents - pharmacology; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Coronary Artery Bypass; Coronary heart disease; Coronary vessels; Cytokines; Cytokines - blood; Cytokines - drug effects; Cytokines - genetics; Enalapril - pharmacology; Genes; Genotype; Heart; Humans; Interleukin-6 - genetics; Losartan - pharmacology; Male; Medical sciences; Middle Aged; Pharmaceuticals; Polymorphism; Polymorphism, Genetic; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2004.05.017

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.