on March 24, 2005
Published online before print March 24, 2005, doi: 10.1161/01.ATV.0000163843.70369.12
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Submitted on December 2, 2004
Accepted on February 13, 2005
Elevated Interleukin-18 Levels Are Associated With the Metabolic Syndrome Independent of Obesity and Insulin Resistance
Joseph Hung *;
From the Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia, and School of Medicine and Pharmacology, University of Western Australia, Perth (J.H., B.M.M., P.L.T.); and Clinical Biochemistry, Western Australian Centre for Pathology and Medical Research (PathCentre), and School of Surgery and Pathology, University of Western Australia, Perth (C.M.L.C., J.P.B.).
* To whom correspondence should be addressed. E-mail: jhung{at}cyllene.uwa.edu.au.
Objective--Activated innate immunity is thought to be involved in the pathogenesis of metabolic syndrome and type 2 diabetes. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response. We sought to determine whether an elevated IL-18 concentration was a risk predictor for metabolic syndrome in a community population independently of obesity and hyperinsulinemia.
Methods and Results--A representative general population, aged 27 to 77 years, without clinical diabetes was studied for clinical and biochemical risk factors for metabolic syndrome. Serum IL-18 concentration measured in 955 subjects correlated with metabolic syndrome traits including body mass index (BMI), waist circumference, triglyceride, high-density lipoprotein (inversely), and fasting glucose and insulin levels (all P<0.001). Mean IL-18 levels rose progressively with increasing number of metabolic risk factors (ANOVA P<0.001). After adjusting for age, gender, BMI, and insulin levels, increasing IL-18 tertiles were associated with an odds ratio for metabolic syndrome of 1.0, 1.42, and 2.28, respectively (P trend=0.007). The graded risk relation was even stronger in nonobese subjects and not attenuated when adjusted for C-reactive protein and IL-6 levels.
Conclusion--Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome.
Key words: IL-18 • metabolic syndrome • obesity • insulin resistance • inflammatory mediators
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