Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose.

BACKGROUND

The metabolic syndrome (MetS) is a cluster of risk factors that are highly associated with increased risk for cardiovascular disease (CVD). Increased serum levels of plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6) and IL-18 have been reported to be associated with CVD. Recently, IL-18 has been shown to be predictive for cardiovascular events in subjects with MetS. We have investigated the expression of PAI-1, IL-6 and IL-18 in subcutaneous adipose tissue (AT) of subjects with (n = 22) and without (n = 36) MetS. Furthermore, we have analysed the expression of IL-18 in monocyte-derived macrophages (MDMs) in an in vitro model of hyperglycaemia.

METHODS

We studied the expression of PAI-1, IL-6 and IL-18 in biopsies of subcutaneous adipose tissue using Real-time PCR. After isolation and cultivation of MDMs, expression of IL-18 was determined by Real-time PCR.

RESULTS

Expression of IL-18 was increased in subcutaneous AT of subjects with MetS (p < 0.05). Multivariate analysis revealed fasting plasma glucose to be the only MetS component being independently associated with expression of IL-18 in AT (p < 0.05). Exposure to hyperglycaemia, increased in expression of IL-18 in MDMs (p < 0.01).

CONCLUSION

Our findings suggest that subjects with MetS have a particular inflammatory pattern in AT, possibly driven by fasting glucose. MDMs might - at least in part - be the cellular source of this increased expression. Together with recent reports, showing IL-18 to be predictive for cardiovascular events, our findings could provide the basis for further research of the role of IL-18 as a link and possible target in the association between MetS and atherosclerosis.