Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance.
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 independent of obesity and hyperinsulinemia.


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 the 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.


CONCLUSIONS
Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome.
Hung
Joseph
J
Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia, and School of Medicine and Pharmacology, University of Western Australia, Nedlands, Perth. jhung@cyllene.uwa.edu.au
McQuillan
Brendan M
BM
Chapman
Caroline M L
CM
Thompson
Peter L
PL
Beilby
John P
JP
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology*; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D011237:Predictive Value of Tests; D012307:Risk Factors
D015415:Biomarkers; D020382:Interleukin-18; D015850:Interleukin-6; D002097:C-Reactive Protein