Absence of detectable IL-1beta 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-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.
University Department of Pharmacology, Oxford, United Kingdom.
D T
DT
Walsh
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S
Betmouni
V H
VH
Perry
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D011328:Prions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase