IL-1, quo vadis?

The build up of lipids and immune cells in the subintimal pace of arteries is termed atherosclerosis. This slow, but proressive process occurs in the majority of humans. Atherosclerosis emains undetected until changes in the atherosclerotic vessel ause decreased blood flow, or result in luminal thrombotic occluion. It is generally accepted that elevated blood cholesterol levels lay a causative role in the pathogenesis of atherosclerosis. Why he excessive lipid deposition in atherosclerotic lesions is accomanied by an elaborate inflammatory response however, is far less nderstood. A myriad of cytokines, chemokines and other factors as been shown to influence the inflammatory reaction toward he buildup of lipids and some of these factors can modulate the nsuing architectural changes of the arteries [1]. Interleukin (IL)-1 cytokines play a pivotal role in triggering vesel wall inflammation. The biological activity of IL-1 cytokines is ontrolled by a naturally occurring IL-1 receptor antagonist (ILra). IL-1ra binds to the IL-1 receptor (IL-1R) but does not induce ts activation. IL-1ra counterbalances the proinflammatory activity f IL-1 cytokines by competing with IL-1 and IL-1 for binding o the IL-1R. Genetic studies have highlighted the importance of a nely tuned IL-1R activation for the arterial vascular system. The bsence of IL-1ra leads to a prolific, and ultimately, a lethal arterial nflammation which is most pronounced in areas of high blood flow urbulences [2]. This suggests that physical stress, such as shear tress, leads to the induction of an IL-1 response in the vessel wall, hich is normally counterbalanced by IL-1ra. Of note, the same reas that show persistent and damaging inflammation in the ILra deficient mice are the predilection sites for the development of