Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis.
Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis.
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DOI：
10.1161/jaha.112.002006
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发表时间：
2012-06
影响因子：
5.4
通讯作者：
Rothwell NJ
中科院分区：
文献类型：
--
作者：
Denes A;Drake C;Stordy J;Chamberlain J;McColl BW;Gram H;Crossman D;Francis S;Allan SM;Rothwell NJ
全身性炎症通过尚不清楚的机制促进脑血管疾病的脑病理学。在这里，我们表明，动脉粥样硬化，一种主要的全身性炎症性疾病，与严重的脑血管炎症小鼠，这种影响是由促炎细胞因子白细胞介素-1（IL-1）介导的。喂食Paigen或西方饮食的载脂蛋白E缺陷小鼠发生血管炎症、小胶质细胞活化和脑中白细胞募集，这些在载脂蛋白E缺陷小鼠与IL-1 1 1型受体缺陷小鼠杂交中不存在。用抗IL-1β抗体全身中和IL-1β可逆转主动脉斑块形成（Paigen组为34%，西方饮食组为45%），并减少外周器官中的炎性细胞因子表达。通过IL-1β抗体给药逆转了脉络丛中的中央脂质蓄积相关白细胞浸润。喂食西方饮食的动物显示脑中的血管炎症比喂食Paigen饮食的小鼠低57%，并且在施用IL-1β抗体后进一步降低24%。这些结果表明，IL-1是全身介导的脑血管炎症的关键驱动因素，针对IL-1β的干预措施可能对动脉粥样硬化、痴呆或中风有治疗作用。（J Am Heart Assoc.2012;1：e002006 doi：10.1161/JAHA.112.002006.）
Systemic inflammation contributes to brain pathology in cerebrovascular disease through mechanisms that are poorly understood. 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. 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.)