Expression of interleukin-18 in human atherosclerotic plaques and relationto plaque instability

Background-Interleukin (IL)-18 is a potent proinflammatory cytokine with po tential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown. Methods and Results-In the present study, we examined stable and unstable h uman carotid atherosclerotic plaques retrieved by endarterectomy for the pr esence of IL-18 using reverse transcription-polymerase chain reaction (PCR) , Western blot, and immunohistochemical techniques. IL-18 was highly expres sed in the atherosclerotic plaques compared with control normal arteries an d was localized mainly in plaque macrophages. IL-18 receptor was also upreg ulated in plaque macrophages and endothelial cells, suggesting potential bi ological effects. To examine the role of IL-18 in atherosclerosis, we deter mined the relation between IL-18 mRNA expression and signs of plaque instab ility using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asy mptomatic (stable) plaques (P <0.01). Conclusions-These results suggest, for the first time, a major role for IL- 18 in atherosclerotic plaque destabilization leading to acute ischemic synd romes.