Interleukin‐1 Mediates Neuroinflammatory Changes Associated With Diet‐Induced Atherosclerosis

Background Systemic inflammation contributes to brain pathology in cerebrovascular disease through mechanisms that are poorly understood. Methods and Results Here we show that atherosclerosis, a major systemic inflammatory disease, is associated with severe cerebrovascular inflammation in mice and that this effect is mediated by the proinflammatory cytokine interleukin‐1 (IL‐1). Apolipoprotein E–deficient mice fed Paigen or Western diets develop vascular inflammation, microglial activation, and leukocyte recruitment in the brain, which are absent in apolipoprotein E–deficient mice crossed with IL‐1 type 1 receptor–deficient mice. Systemic neutralization of IL‐1β with an anti–IL‐1β antibody reversed aortic plaque formation (by 34% after a Paigen and 45% after a Western diet) and reduced inflammatory cytokine expression in peripheral organs. Central, lipid accumulation–associated leukocyte infiltration into the choroid plexus was reversed by IL‐1β antibody administration. Animals fed a Western diet showed 57% lower vascular inflammation in the brain than that of mice fed a Paigen diet, and this was reduced further by 24% after IL‐1β antibody administration. Conclusions These results indicate that IL‐1 is a key driver of systemically mediated cerebrovascular inflammation and that interventions against IL‐1β could be therapeutically useful in atherosclerosis, dementia, or stroke. (J Am Heart Assoc. 2012;1:e002006 doi: 10.1161/JAHA.112.002006.)