IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN-γ and CXCL16 Expression Independently of T Cells

Abstract

Objective-The proatherogenic effect of IL-18 is shown to be dependent on IFN-␥ production. It is believed that activated T cells play a proatherogenic role through secretion of IFN-␥. However, recent studies in vitro have shown that macrophages, NK cells, and even vascular smooth muscle cells may also secrete IFN-␥ after stimulation by cytokines like IL-18. We therefore investigated whether cells other than activated T cells can play a proatherogenic role via IFN-␥ secretion under the stimulation of IL-18 in vivo. Methods and Results-SCID/apoE knockout mice were injected intraperitoneally with either IL-18 or phosphate-buffered saline 3 times per week for 7 weeks. Our results show that administration of IL-18 leads to 3-fold larger lesions and 2-fold higher circulating IFN-␥ despite the absence of T cells. In addition, increased IFN-␥, accompanied by elevation of the scavenger receptor/chemokine CXCL16, was observed in both lesions and spleens.

When Interleukin-18 Conducts, the Preludio Sounds the Same no Matter Who Plays

“…27 In this issue, an elegant study by Tenger et al demonstrates that the proatherogenic role of IL-18 goes beyond its effect on the Th1 polarization, because IL-18 -mediated acceleration of atherosclerosis is detected in apoE Ϫ/Ϫ /SCID mice in the absence of T cells. 1 The authors show that IL-18 -induced IFN-␥ production in macrophages and NK cells is accompanied by an upregulation of the CXCL16 scavenger receptor in lesions. This cascade of events is likely to be responsible for increased foam cell formation and fatty streak development under IL-18 treatment.…”

CXCL16 in Vascular Pathology Research: from Macro Effects to microRNAs

“…In ApoE / mice treated only with IL-18, which is known to be an inducer of INF , a similar effect occurred as when they were subjected to direct INF treatment. In this way, it was demonstrated that CXCL16 mRNA expression could be also indirectly triggered 30) . All these findings reflect the complexity of the CXCL16 regulation pathway, which could be modified on different levels of the CXCL16 gene regulatory network.…”

Reduction of Pro-Inflammatory Cytokines through Hemodiafiltration

“…[36] It plays a critical role in atherosclerosis in ESRD patients. [37][38][39] Mallat et al had found that IL-18 binding protein can reduce atherosclerosis. [40] In our study, the plasma IL-18 level was reduced after six months of HDF, which may result in less IL-18 related atherosclerosis.…”