IL-18 accelerates atherosclerosis accompanied by elevation of IFN-γ and CXCL16 expression independently of T cells

Charlotta Tenger, Anna Sundborger, Jacek Jawien, Xinghua Zhou

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Objective - The proatherogenic effect of IL-18 is shown to be dependent on IFN-γ production. It is believed that activated T cells play a proatherogenic role through secretion of IFN-γ. However, recent studies in vitro have shown that macrophages, NK cells, and even vascular smooth muscle cells may also secrete IFN-γ after stimulation by cytokines like IL-18. We therefore investigated whether cells other than activated T cells can play a proatherogenic role via IFN-γ 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-γ despite the absence of T cells. In addition, increased IFN-γ, 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-γ 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-γ secreted by macrophages, NK cells, and vascular cells is sufficient for the disease progression.

Original languageEnglish (US)
Pages (from-to)791-796
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Keywords

  • Atherosclerosis
  • Cytokines
  • Macrophages
  • NK cells
  • Scavenger receptors

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