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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:791.)
© 2005 American Heart Association, Inc.

Atherosclerosis & Lipoproteins

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

Charlotta Tenger; Anna Sundborger; Jacek Jawien; Xinghua Zhou

From the Centre for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Xinghua Zhou, MD, PhD, FESC, Centre for Molecular Medicine L8:03, Karolinska Hospital, S-17176 Stockholm, Sweden. E-mail Xinghua.Zhou{at}cmm.ki.se

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. Furthermore, our findings revealed that macrophages, NK cells, and vascular cells were the source of IFN- under the stimulation of IL-18 in the absence of T cells in vivo.

Conclusion— The current data suggest that the proatherogenic effect of IL-18 can occur in the absence of T cells and that IFN- secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression.

To investigate whether cells other than T cells play a proatherogenic role via secretion of IFN-, we used SCID/apoE knockout mice. Administration of IL-18 resulted in larger lesions and elevated IFN-. Our data suggest that IFN- from macrophages, NK cells, and vascular cells in vivo is sufficient for the disease progression.

Key Words: atherosclerosis • cytokines • macrophages • NK cells • scavenger receptors

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