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Journal of Virology, April 2005, p. 5174-5184, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5174-5184.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease

Colm Cunningham,^* David C. Wilcockson, Delphine Boche, and V. Hugh Perry

CNS Inflammation Group, Southampton Neuroscience Group, School of Biological Sciences, Southampton, Hampshire, United Kingdom

Received 27 August 2004/ Accepted 24 November 2004

Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrP^Sc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrP^Sc deposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and ₂-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrP^Sc deposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrP^Sc is not a stimulus for splenic macrophages and that neither peripheral PrP^Sc deposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.

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* Corresponding author. Mailing address: CNS Inflammation Group, School of Biological Sciences, Bassett Crescent East, Southampton, Hampshire SO16 7PX, United Kingdom. Phone: (44) 023 80597642. Fax: (44) 023 80592711. E-mail: C.Cunningham{at}soton.ac.uk.

C.C. and D.C.W. contributed equally to this work.

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Journal of Virology, April 2005, p. 5174-5184, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5174-5184.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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