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

• DOI: 10.1161/atvbaha.107.149245
• Publication Date: 2007-10-19T23:00:36Z
• Authors: Simon R. Thompson; Daniela Novick; Carmel J. Stock; Julie Sanders; David Brull; Jackie Cooper; Patricia Woo; George Miller; Menachem Rubinstein; Steve E. Humphries
• Keywords: Male; 0301 basic medicine; Interleukin-18; Myocardial Infarction; Coronary Disease; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; Europe; 03 medical and health sciences; Phenotype; Postoperative Complications; Gene Frequency; Haplotypes; Risk Factors; Case-Control Studies; Humans; Intercellular Signaling Peptides and Proteins; Genetic Predisposition to Disease; Prospective Studies; Coronary Artery Bypass; Aged; Follow-Up Studies

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 Hap III 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 Hap III 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.