When interleukin-18 conducts, the Preludio sounds the same no matter who plays.

The first event in atherogenesis is the extravasation of lipoproteins into the subintimal layers of arteries, where they are trapped by extracellular matrix molecules such as proteoglycans and undergo oxidative modifications that in turn lead to endothelial cell activation and local recruitment of inflammatory cells. The monocyte-derived macrophages transform into foam cells by an unlimited upload of oxidized lipoproteins. Foam cells accumulated in the subintimal space constitute the fatty streaks. During this process, macrophages become activated and release a number of cytokines and proteases, which perpetuate the local inflammatory environment. It is now recognized that such a chronic inflammatory process is the fundamental pathogenic mechanism of atherogenesis. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Tenger et al address the role of a key molecule, interleukin (IL)-18, in the regulation of this inflammatory condition.1