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Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis

Denes, A and Drake, C and Stordy, J and Chamberlain, J and Gram, Hermann and Crossman, D and Francis, S and Rothwell, N (2012) Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis. Journal of the American Heart Association, 1 (3). e002006. ISSN 2047-9980

Abstract

Systemic inflammatory processes contribute to brain pathology in cerebrovascular disease through mechanisms which 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 pro-inflammatory cytokine interleukin-1 (IL-1). Apolipoprotein E deficient (ApoE-/-) mice fed Paigen or Western diet develop vascular inflammation, microglial activation and leukocyte recruitment in the brain, which are absent in ApoE-/- mice crossed with IL-1 type 1 receptor deficient mice (IL-R1-/-) mice. Systemic neutralisation of IL-1β with an anti-IL-1β antibody reversed aortic plaque formation and reduced inflammatory cytokine expression in peripheral organs. In the brain, vascular inflammation and leukocyte infiltration into the choroid plexus were reversed by IL-1β blockade in animals fed a Paigen diet.
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

Item Type: Article
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Keywords: IL-1, brain, atherosclerosis
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6676

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