Denes, A., Drake, C., Stordy, J. et al. (7 more authors) (2012) Interleukin-1 Mediates Neuroinflammatory Changes Associated With Diet-Induced Atherosclerosis. Journal of the American Heart Association, 1 (3). e002006. ISSN 2047-9980
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.)
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012 The Authors. Journal of the American Heart Association published by Wiley-Blackwell on behalf of American Heart Association, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/3.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
Keywords: | interleukin-1; atherosclerosis; cerebrovascular inflammation; leukocyte; microglia |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Jul 2016 13:31 |
Last Modified: | 20 Jul 2016 13:31 |
Published Version: | http://dx.doi.org/10.1161/JAHA.112.002006 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1161/JAHA.112.002006 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101835 |
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