Role of Interleukin-18 in Destabilization of the Atherosclerotic Plaque in Humans

Abstract

Precise location of IL-18 in cell and tissue elements of the atherosclerotic lesions in humans and its role in destabilization of the atherosclerotic plaque were detected. The data suggested a hypothesis on indirect involvement of IL-18 in destruction of the elastic and collagen fibers in an unstable plaque due to this cytokine capacity to induce the production of IFN-γ in T cells and macrophages, this eventually leading to inhibition of collagen and elastin synthesis in smooth muscle cells of the vascular wall and to loosening of the plaque cap.

Interleukin-18 and Atherosclerosis: Mediator or Biomarker

“…These authors have precisely demonstrated the location of IL-18 in the cellular and tissue elements of unstable and stable atherosclerotic plaques, whereas no IL-18 was observed in control vascular tissue. Intracellular (endotheliocytes, macrophages/monocytes) and diffuse extracellular IL-18 was shown to be located mainly in unstable lesions [37], which clearly demonstrated the importance of IL-18.…”

“…In an another study, the myocardium of patients with ischemic heart failure express the alpha chain of the IL-18 receptor and have elevated levels of circulating IL-18 levels and has been shown to be correlated with death [15]. Very recently, [37] have demonstrated role of interleukin 18 in destabilization of the atherosclerotic plaque in humans. These authors have precisely demonstrated the location of IL-18 in the cellular and tissue elements of unstable and stable atherosclerotic plaques, whereas no IL-18 was observed in control vascular tissue.…”

“…Moreover, a neutralizing antibody to IL-18 resulted in near prevention of endotoxin-induced myocardial suppression in mice [34]. In addition, in animal model, IL-18 administration has been demonstrated to result in ventricular hypertrophy and elevated left ventricular diastolic pressure [35,36].…”

Detection of Atherosclerotic Plaques in the Rabbit Aorta Using Ultrasound Microbubbles Conjugated to Interleukin-18 Antibodies

“…Specifically, IL-18 induces T cells and natural killer (NK) cells to produce IFN-γ and promotes the differentiation of T cells into Th1 cells to enhance the cell-mediated immune response. In addition, IL-18 induces the expression of IL-8, TNF-α, and adhesion molecules, which promote atherosclerotic plaque rupture [ 23 ].…”

Biomarkers for unstable atherosclerotic plaques in carotid arteries

“…IL-6 is associated with presence of carotid plaques and plaque instability (26, 38,41). There are some hypothesis that IL-23 and IL-27 are also increased in carotid atherosclerosis (42,43) and IL-18 is connected with plaque destabilization (44). Still their role and action in the inflammation and plaque development is not clear.…”