Components of the interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness

Abstract

Objective: The metabolic syndrome (MetS) is an increasing epidemiologic challenge and cardiovascular risk factor. Interleukin-6 (IL-6) is a cytokine that exerts its biological function via a complex orchestration of soluble and membrane bound receptors. We have investigated associations between IL-6 and its soluble receptors, soluble IL-6 receptor (sIL-6r) and soluble glycoprotein 130 (sGP130) and the metabolic syndrome. Furthermore, we have investigated possible associations with endothelial dysfunction and arterial stiffness.

Methods: A total of 563 subjects were included in this study. The Adult Treatment Panel III criteria of the National Cholesterol Education Program were used for the definition of MetS. We used commercially available ELISA to analyse circulating levels of the markers. Pulse wave propagation time (PWP) was determined to assess arterial stiffness.

Results: The criteria for having MetS were filled by 221 subjects. sGP130, sIL-6r and IL-6 levels were elevated in subjects with MetS (p<0.05 for all markers), and are associated with increasing components of MetS. Particularly hypertriglyceridaemia, hypertension and fasting plasma glucose (FPG) seem to carry this association. sGP130 (p<0.01), IL-6 (p<0.05) and partially sIL-6r (p<0.05) correlated with markers of endothelial function (E-selectin, I-CAM-1, V-CAM-1) and inversely with PWP after adjustment for relevant covariates.

Conclusion: sGP130, sIL-6r and IL-6 were significantly elevated in subjects with MetS. In addition, sGP130, IL-6 and partially sIL-6r were associated with markers of endothelial function and arterial stiffness. This finding sheds new light on the role of these inflammatory cytokines in subjects with MetS and the development and progression of clinically silent atherosclerosis.

Trial registration: ClinicalTrials.gov NCT00764010.