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Arteriosclerosis, Thrombosis, and Vascular Biology
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Published Online
on October 19, 2007

Arteriosclerosis, Thrombosis, and Vascular Biology. 2007
Published online before print October 19, 2007, doi: 10.1161/ATVBAHA.107.149245
A more recent version of this article appeared on December 1, 2007
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Submitted on June 4, 2007
Accepted on September 5, 2007

Free Interleukin (IL)-18 Levels, and the Impact of IL18 and IL18BP Genetic Variation, in CHD Patients and Healthy Men

Simon R. Thompson ; Daniela Novick ; Carmel J. Stock ; Julie Sanders ; David Brull ; Jackie Cooper ; Patricia Woo ; George Miller ; Menachem Rubinstein ; and Steve E. Humphries *

From Cardiovascular Genetics (S.R.T., J.C., S.E.H.), Rayne Institute, University College London, UK.; the Department of Molecular Genetics (D.N., M.R.), The Weizmann Institute of Science, Rehovot, Israel; the Department of Immunology and Molecular Pathology (C.J.S., P.W.), University College London, UK; UCL Department of Surgery (J.S.), The Heart Hospital, Westmoreland Street, London, UK; Clinical and Academic Department of Cardiovascular Medicine (D.B.), The Whittington Hospital NHS Trust, London, UK; and the Medical Research Council Cardiovascular Group (G.M.), Wolfson Institute of Preventive Medicine, London, UK.

* To whom correspondence should be addressed. E-mail: rmhaseh{at}ucl.ac.

Objective—To investigate free interleukin-18 (fIL-18) levels, and variation within the IL-18 system genes, in heart surgery patients, and healthy men.

Methods and Results—fIL-18 was calculated from IL-18 and IL-18 binding protein (BP) levels, in 421 healthy men and 196 post–coronary artery bypass graft (CABG) patients. After surgery, fIL-18 peaked at 6 hours (from 117 to 331 pg/mL) but fell to below presurgery levels at 24 hours (99 pg/mL), because of changes in total IL-18 and IL-18BP. fIL-18 24 hours postsurgery was significantly higher in those who suffered a major complication after surgery (125 versus 80 pg/mL, P<0.01). Baseline total IL-18 was also higher in healthy men who went on to suffer an MI over 17 years of prospective study (276 versus 240 pg/mL, P=0.01). Tagging SNPs for IL18 (n=5) and IL18BP (n=3) were determined, in both studies the IL18 HapIII haplotype (frequency 30%) was associated with 36% lower baseline fIL-18 levels before surgery (P<0.01), and 7% lower in healthy men (P=0.04). The frequency of HapIII was lower in CABG patients than in healthy men (20.7 versus 29.8%, P<0.01).

Conclusions—IL-18 levels, which are determined in part by variation in IL18, play a role in CHD development and postsurgery outcome.
Key words: IL-18 • IL-18BP • polymorphism • surgery • atherosclerosis






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