NR AMET
AU Walsh,D.T.; Betmouni,S.; Perry,V.H.
TI Absence of detectable IL-1ß production in murine prion disease: a model of chronic neurodegeneration.
QU Journal of Neuropathology and Experimental Neurology 2001 Feb; 60(2): 173-82
PT journal article
AB Murine prion disease is accompanied by a modified inflammatory response characterized by early but prolonged microglial activation and T-lymphocyte recruitment. In this model, we look at the profile of cytokine production, particularly IL-1ß. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease. We were unable to detect any IL-1ß using immunohistochemistry, with various fixation protocols, or ELISA between 8 and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1ß, IL-6, IFNgamma, and iNOS as measured by quantitative RT-PCR. Using the same procedures and examining tissues at the same time, IL-1ß immunostaining was detected in infiltrating inflammatory cells in mouse brains injected with LPS or in a delayed-type hypersensitivity response in the brain. Soluble IL-1ß was also increased, as measured by ELISA, and there was an increase in mRNA species for IL-1ß, IL-6, TNFalpha but not IFNgamma or iNOS in these brains. These data reveal that chronic neurodegeneration seen in prion disease does not induce production of a range of proinflammatory mediators despite showing marked microglial activation and raise the question as to whether IL-1ß would exacerbate the neurodegeneration as it does in acute neurodegeneration following head injury and stroke.
MH Animal; Brain/*metabolism/pathology; Disease Models, Animal; Encephalitis/metabolism/pathology/physiopathology; Interferon Type II/genetics; Interleukin-1/*metabolism; Interleukin-6/genetics; Mice; Mice, Inbred C57BL; Microglia/pathology; Nerve Degeneration/*metabolism/pathology; Neurons/metabolism/pathology; Nitric-Oxide Synthase/genetics; Prion Diseases/*metabolism/pathology; Prions/pharmacology; RNA, Messenger/metabolism; Support, Non-U.S. Gov't; Tumor Necrosis Factor/genetics
AD University Department of Pharmacology, Oxford, United Kingdom.
SP englisch
PO USA