title: Atypical inflammation in the central nervous system in prion disease.
abstract: The inflammatory response in prion diseases is dominated by microglial activation. Contrary to their profile in vitro none of the pro-inflammatory cytokines interleukin-1beta, interleukin-6, or tumour necrosis factor-alpha are significantly upregulated in the ME7 model of prion disease. However, two major inflammatory mediators are elevated: transforming growth factor-beta1 and prostaglandin E2. This cytokine profile is the same as that reported for macrophages during phagocytosis of apoptotic cells and indeed transforming growth factor-beta1 and prostaglandin E2 are responsible for the downregulated phenotype of these macrophages. Transforming growth factor-beta1 may also have roles in extracellular matrix deposition and in amyloidogenesis and may play a direct role in disease pathogenesis. There is also now evidence to suggest that a peripheral infection, and its consequent systemic cytokine expression, may drive central nervous system cytokine expression and perhaps exacerbate disease.
authors.affiliation: CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK. vhp@soton.ac.uk
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Colm
authors.initials: C
authors.lastname: Cunningham
authors.forename: Delphine
authors.initials: D
authors.lastname: Boche
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017096:Prion Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D015232:Dinoprostone