title: Interleukin-1 mediates neuroinflammatory changes associated with diet-induced atherosclerosis.
abstract: BACKGROUND
  Systemic inflammation contributes to brain pathology in cerebrovascular disease through mechanisms that are poorly understood.
  
  
  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.).
authors.affiliation: Faculty of Life Sciences, University of Manchester,  Manchester, UK (A.D., C.D., S.M.A., N.J.R.).
authors.forename: Adam
authors.initials: A
authors.lastname: Denes
authors.forename: Caroline
authors.initials: C
authors.lastname: Drake
authors.forename: Jing
authors.initials: J
authors.lastname: Stordy
authors.forename: Janet
authors.initials: J
authors.lastname: Chamberlain
authors.forename: Barry W
authors.initials: BW
authors.lastname: McColl
authors.forename: Hermann
authors.initials: H
authors.lastname: Gram
authors.forename: David
authors.initials: D
authors.lastname: Crossman
authors.forename: Sheila
authors.initials: S
authors.lastname: Francis
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Allan
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
keywords: atherosclerosis; cerebrovascular inflammation; interleukin-1; leukocyte; microglia