Objective-Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1␤ (IL-1␤), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis. Methods and Results-We generated mice lacking both apoE and IL-1␤. The sizes of atherosclerotic lesions at the aortic sinus in apoEϪ/Ϫ/IL-1␤Ϫ/Ϫmice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoEϪ/Ϫ/IL-1␤ ϩ/ϩ mice, and the percentage of the atherosclerotic area to total area of apoEϪ/Ϫ/IL-1␤Ϫ/Ϫ at 24 weeks of age also showed a significant decrease of about 30% compared with apoEϪ/Ϫ/IL-1␤ ϩ/ϩ . The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoEϪ/Ϫ/ IL-1␤Ϫ/Ϫ aorta were significantly reduced compared with the apoEϪ/Ϫ/IL-1␤ ϩ/ϩ . Furthermore, VCAM-1 was also reduced at the protein level in apoEϪ/Ϫ/IL-1␤Ϫ/Ϫ aorta compared with apoEϪ/Ϫ/IL-1␤ ϩ/ϩ . Conclusions-The

No abstract

These findings demonstrate that IFN-gamma produced by bone marrow-derived cells delays the progression of atherosclerosis without any effect on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.