Absence of detectable IL-1β production in murine prion disease: a model of chronic neurodegeneration

DT Walsh, S Betmouni, VH Perry - Journal of Neuropathology & …, 2001 - academic.oup.com
DT Walsh, S Betmouni, VH Perry
Journal of Neuropathology & Experimental Neurology, 2001academic.oup.com
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-1β. Mice inoculated with prion-
infected brain homogenate show typical signs of prion disease. We were unable to detect
any IL-1β using immunohistochemistry, with various fixation protocols, or ELISA between 8
and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1β, IL-6, IFNγ, and …
Abstract
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-1β. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease. We were unable to detect any IL-1β using immunohistochemistry, with various fixation protocols, or ELISA between 8 and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1β, IL-6, IFNγ, and iNOS as measured by quantitative RT-PCR. Using the same procedures and examining tissues at the same time, IL-1β 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-1β was also increased, as measured by ELISA, and there was an increase in mRNA species for IL-1β, IL-6, TNFα but not IFNγ 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-1β would exacerbate the neurodegeneration as it does in acute neurodegeneration following head injury and stroke.
Oxford University Press