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Review
. 2010 Mar 23:9:11.
doi: 10.1186/1475-2840-9-11.

The role of interleukin-18 in the metabolic syndrome

Marius Trøseid  1 , Ingebjørg Seljeflot, Harald Arnesen
Affiliations
Review

The role of interleukin-18 in the metabolic syndrome

Marius Trøseid et al. Cardiovasc Diabetol. .

Abstract

The metabolic syndrome is thought to be associated with a chronic low-grade inflammation, and a growing body of evidence suggests that interleukin-18 (IL-18) might be closely related to the metabolic syndrome and its consequences. Circulating levels of IL-18 have been reported to be elevated in subjects with the metabolic syndrome, to be closely associated with the components of the syndrome, to predict cardiovascular events and mortality in populations with the metabolic syndrome and to precede the development of type 2 diabetes. IL-18 is found in the unstable atherosclerotic plaque, in adipose tissue and in muscle tissue, and is subject to several regulatory steps including cleavage by caspase-1, inactivation by IL-18 binding protein and the influence of other cytokines in modulating its interaction with the IL-18 receptor. The purpose of this review is to outline the role of IL-18 in the metabolic syndrome, with particular emphasis on cardiovascular risk and the potential effect of life style interventions.

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Figures

Figure 1
Figure 1
Regulation and biological effects of interleukin-18. The cytokine is expressed as a precursor, pro-IL-18, which is inactive until cleaved by caspase-1. Once secreted, IL-18 is bound and inactivated by IL-18 binding protein (IL-18 BP), and only the free fraction can stimulate a signal transduction via the β-chain of the IL-18 receptor (IL-18R). The biological effect is dependent on the cytokine milieu: IL-18 may stimulate a Th2 response in combination with IL-2, and may act synergistically with IL-12 to stimulate a Th1 response with production of IFN-γ, a central feature of the atherosclerotic lesion.
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