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- PMID: 23130147
- UKPMCID: 23130147
- DOI: 10.1161/JAHA.112.002006
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Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis.
Denes, Adam; Drake, Caroline; Stordy, Jing; Chamberlain, Janet; McColl, Barry W; Gram, Hermann; Crossman, David; Francis, Sheila; Allan, Stuart M; Rothwell, Nancy J
Journal of the American Heart Association. 2012;1(3):e002006.
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Full-text held externally
- PMID: 23130147
- UKPMCID: 23130147
- DOI: 10.1161/JAHA.112.002006
Abstract
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.).