Inhibition of peripheral TNF can block the malaise associated with CNS inflammatory diseases
Open accessAbstract
Circulating cytokine levels are elevated in many neuropathologies and may be a cause of the associated malaise and depression. Using a rat model, we demonstrate that sickness behaviors generated by microinjection of IL-1beta into the anterior hypothalamus are adopted by naive recipient animals following plasma transfer. We further show that neutralizing peripheral TNF by etanercept (a p75 TNF receptor/Fc fusion protein) prior to the IL-1beta microinjection inhibits certain IL-1beta-mediated sickness behaviors, such as the depression of open-field activity and reduced glucose consumption. IL-1beta-induced central lesions induce peripheral TNF as part of the acute-phase response, and this appears to be the principal target of the etanercept. Thus behavioral changes induced by CNS lesions may result from peripheral expression of cytokines that can be targeted with drugs which do not need to cross the blood-brain barrier to be efficacious.
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Blockade of TNF-α production at the periphery prevented histological lesions induced by IL-1β in CNS.
“Recently, it was demonstrated that a blockade of TNF-α production at the periphery prevented histological lesions induced by IL-1β in CNS [157].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [157]
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- Authors
- Jiang, Y., Deacon, R., Anthony, D. C., & Campbell, S. J.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Campbell, S.J.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 32
- Issue
- 1
- Pages
- 125-132
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2008779800
- Cited by
- 64
- References
- 3
- Citations by year
- 2026: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 9 · 2015: 6 · 2014: 1 · 2013: 8 · 2012: 11
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- sickness behavior, TNF inhibition, etanercept, IL-1β, anterior hypothalamus, plasma transfer, depression, malaise, acute phase response, peripheral cytokines, glucose utilization, open field behavior, neuroinflammation
- MeSH terms
- Etanercept, Animals, Behavior, Animal, Central Nervous System Diseases, Exploratory Behavior, Humans, Immunoglobulin G, Inflammation, Male, Tumor Necrosis Factor-alpha, Rats, Wistar, Receptors, Tumor Necrosis Factor, Inflammation Mediators, Rats, Interleukin-1beta
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