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

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-1[beta]. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease. We were unable to detect any IL-1[beta] using immunohistochemistry, with various fixation protocols, or ELISA between 8 and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1[beta], IL-6, IFN[gamma], and iNOS as measured by quantitative RT-PCR. Using the same procedures and examining tissues at the same time, IL-1[beta] 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-1[beta] was also increased, as measured by ELISA, and there was an increase in mRNA species for IL-1[beta], IL-6, TNF[alpha] but not IFN[gamma] 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-1[beta] would exacerbate the neurodegeneration as it does in acute neurodegeneration following head injury and stroke