Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol

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.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 5.53). 06/2005; 25(6):1268-73. DOI: 10.1161/01.ATV.0000163843.70369.12
Source: PubMed

ABSTRACT 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.
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.
Our findings support the hypothesis that activation of IL-18 is involved in the pathogenesis of the metabolic syndrome.

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    • "Significantly, circulating IL-18 is elevated in obesity [17], metabolic syndrome [18] and T2DM [19] [20] and elevated IL-18 in T2DM is associated with the development of important clinical complications such a nephropathy [21] and atherosclerosis [22]. In common with IL-1b, IL-18 is synthesised as a pro-peptide which lacks a secretory signal and therefore requires proteolytic processing prior to secretion; this is achieved by casapse-1 [16]. "
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    Cytokine 02/2014; 65(2):222-30. DOI:10.1016/j.cyto.2013.10.008 · 2.87 Impact Factor
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    • "Footnote: statistics were performed by Student's t-test, * P < 0.05. IL18 is proinflammatory and levels are elevated in obesity and type 2 diabetes [30] [31] [32] and are correlated with traits of the metabolic syndrome [33]. Knockout of IL-18 or its receptor results in obesity and insulin resistance [34], and fasting IL-18 levels are reduced following weight loss in humans [35]. "
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    ABSTRACT: The postprandial state is hypothesised to be proinflammatory and prooxidative, but the relative contributions of fat versus carbohydrate are unclear. Therefore, we examined inflammation and oxidative stress responses in serum and skeletal muscle before and after 1000 kcal meals, which were high in either fat or carbohydrate in 15 healthy individuals. Serum and muscle expression of IL6 was elevated 3 hours after each meal, independently of macronutrient composition (P < 0.01). Serum IL18 was decreased after high-fat meal only (P < 0.01). Plasma total antioxidative status and muscle Cu/Zn-superoxide dismutase were decreased after high-carbohydrate meal only (P < 0.05). We conclude that a high-carbohydrate meal may evoke a greater postprandial oxidative stress response, whereas both fat and carbohydrate increased IL6. We speculate that the observed increases in postprandial IL6, without increases in any other markers of inflammation, may indicate a normal IL6 response to enhance glucose uptake, similar to its role postexercise.
    Journal of nutrition and metabolism 02/2012; 2012(5091):238056. DOI:10.1155/2012/238056
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    • "its increased expression may potentiate inflammation, ECM degradation, adverse remodeling, and other related complications. Of note, IL-18 levels are also increased in diabetes and in metabolic syndrome, both major contributing factors for CAD (Hung et al., 2005; Troseid et al., 2009). "
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