The role of interleukin-18 in the metabolic syndrome

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.

Recent Advances on the Role of Cytokines in Atherosclerosis

“…43 Paradoxically, circulating IL-18 levels in obese subjects and in patients with type 2 diabetes are increased and predict cardiovascular events and mortality. 44 In fact, leukocytes isolated from obese or type 2 diabetes patients respond poorly to IL-18 stimulation with IL-18 and show a 50% reduction in the expression of IL-18R ␣ and ␤ chains. 45 …”

TLR2 and IL 18 in obese diabetic patient

“…Furthermore, it was shown that patients with obesity and type 2 diabetes, or even apparent healthy non obese persons (who have insulin resistance) produce significantly less IFN-γ from peripheral blood mononuclear cells (Th1) in response to IL-18 stimulation compared to lean healthy controls, most likely due to reduced expression of the IL-18 receptor βchain, so IL-18 resistance is a potential explanation of elevated IL-18 levels in such patients [24].…”

“…Both TLR2 and TLR4 have been shown to sense free fatty acids; in addition, ceramides, high-mobility group box 1(HMGB1), fetuin-A, heat shock proteins, and modified LDLs can also activate TLR4. TLR2 and TLR4 then signal through MyD88 to activate the NF-κB and MAPK pathways to inhibit insulin signaling through insulin receptor substrate (IRS) serine phosphorylation and to induce the transcription of proinflammatory cytokines, such as TNF and IL-6, as well as pro-IL-1β and proIL-18 [24].…”

Polymorphism, linkage mapping, and association analysis with carcass traits of four porcine candidate genes selected from gene-expression profiles of Czech Large White and Wild Boar muscles

“…It is produced in many different cell types, including macrophages, endothelial cells, vascular smooth muscle cells, dendritic cells, and Kupffer cells (Gerdes et al, 2002;Trøseid et al, 2010). Moreover, IL18 was found to be expressed also in human muscles, but solely in type II fibres, while IL6 was more prominent in type I fibres.…”