Lack of Interleukin-1beta Decreases the Severity of Atherosclerosis in ApoE-deficient Mice

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-1beta (IL-1beta), 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-1beta. The sizes of atherosclerotic lesions at the aortic sinus in apoE-/-/IL-1beta-/-mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE-/-/IL-1beta+/+ mice, and the percentage of the atherosclerotic area to total area of apoE-/-/IL-1beta-/- at 24 weeks of age also showed a significant decrease of about 30% compared with apoE-/-/IL-1beta+/+. The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoE-/-/IL-1beta-/- aorta were significantly reduced compared with the apoE-/-/IL-1beta+/+. Furthermore, VCAM-1 was also reduced at the protein level in apoE-/-/IL-1beta-/- aorta compared with apoE-/-/IL-1beta+/+.

Conclusions: The lack of IL-1beta decreases the severity of atherosclerosis in apoE deficient mice, possibly through increased expressions of VCAM-1 and monocyte chemotactic protein-1 in the aorta.