Absence of detectable IL-1(beta) production in murine prion disease: A model of chronic neurodegeneration

• Published in: Journal of neuropathology and experimental neurology 2001-02, Vol.60 (2), p.173-182
• Main Authors: Walsh, Desmond T, Betmouni, Samar, Perry, V Hugh
• Format: Article
• Language: English
• ISSN: 0022-3069; 1554-6578

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-1beta. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease. We were unable to detect any IL-1beta using immunohistochemistry, with various fixation protocols, or ELISA between 8 and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1beta, IL-6, IFNgamma, and iNOS as measured by quantitative RT-PCR. Using the same procedures and examining tissues at the same time, IL-1beta 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-1beta was also increased, as measured by ELISA, and there was an increase in mRNA species for IL-1beta, 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-1beta would exacerbate the neurodegeneration as it does in acute neurodegeneration following head injury and stroke.