Free Interleukin (IL)-18 Levels, and the Impact of IL18 and IL18BP Genetic Variation, in CHD Patients and Healthy Men
2007
Objective— To investigate free
interleukin-18(fIL-
18) levels, and variation within the IL-
18system genes, in heart surgery patients, and healthy men. Methods and Results— fIL-
18was calculated from IL-
18and IL-
18binding protein (BP) levels, in 421 healthy men and 196 post–coronary artery bypass graft (CABG) patients. After surgery, fIL-
18peaked 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-
18and IL-18BP. fIL-
1824 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-
18was 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 SNPsfor IL18 (n=5) and
IL18BP(n=3) were determined, in both studies the IL18 Hap III haplotype (frequency 30%) was associated with 36% lower baseline fIL-
18levels before surgery ( P <0.01), and 7% lower in healthy men ( P =0.04). The frequency of Hap III was lower in CABG patients than in healthy men (20.7 versus 29.8%, P <0.01). Conclusions— IL-
18levels, which are determined in part by variation in IL18 , play a role in CHD development and postsurgery outcome.
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