on December 16, 2004
Published online before print December 16, 2004, doi: 10.1161/01.ATV.0000153516.02782.65
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Submitted on June 30, 2004
Accepted on November 23, 2004
IL-18 Accelerates Atherosclerosis Accompanied by Elevation of IFN-
and CXCL16 Expression Independently of T Cells
Charlotta Tenger ;
From the Centre for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
* To whom correspondence should be addressed. 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- on 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 1.7-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.
Key words: atherosclerosis • cytokines • macrophages • NK cells • scavenger receptors
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