Source:http://linkedlifedata.com/resource/pubmed/id/17883399
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-12-11
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| pubmed:abstractText |
TNF-alpha has proved to be a successful target in the treatment of many peripheral inflammatory diseases, but the same interventions worsen immune-mediated CNS disease. However, anti-TNF-alpha strategies may offer promise as therapy for non-immune CNS injury. In this study, we have microinjected IL-1beta or lipopolysaccharide (LPS) into the rat brain as a simple model of brain injury and have systemically administered the TNF-alpha antagonist etanercept to discover whether hepatic TNF-alpha, produced as part of the acute-phase response to CNS injury, modulates the inflammatory response in the brain. We report a significant reduction in neutrophil numbers recruited to the IL-1beta- or LPS-challenged brain as a result of TNF-alpha inhibition. We also show an attenuation in the levels of hepatic mRNA including TNF-alpha mRNA and of TNF-alpha-induced genes, such as the chemokines CCL-2, CXCL-5, and CXCL-10, although other chemokines elevated by the injury were not significantly changed. The reduction in hepatic chemokine synthesis results in reduced numbers of circulating neutrophils, and also a reduction in the numbers recruited to the liver as a consequence of brain injury. These findings suggest that TNF-alpha inhibitors may reduce CNS inflammatory responses by targeting the hepatic acute-phase response, and thus therapies for brain injury need not cross the blood-brain barrier to be effective.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNFR-Fc fusion protein,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1471-4159
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
103
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2245-55
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| pubmed:meshHeading |
pubmed-meshheading:17883399-Acute Disease,
pubmed-meshheading:17883399-Acute-Phase Reaction,
pubmed-meshheading:17883399-Animals,
pubmed-meshheading:17883399-Brain,
pubmed-meshheading:17883399-Brain Injuries,
pubmed-meshheading:17883399-Chemokines,
pubmed-meshheading:17883399-Disease Models, Animal,
pubmed-meshheading:17883399-Encephalitis,
pubmed-meshheading:17883399-Gene Expression Regulation,
pubmed-meshheading:17883399-Immunoglobulin G,
pubmed-meshheading:17883399-Immunosuppressive Agents,
pubmed-meshheading:17883399-Inflammation Mediators,
pubmed-meshheading:17883399-Liver,
pubmed-meshheading:17883399-Male,
pubmed-meshheading:17883399-Rats,
pubmed-meshheading:17883399-Rats, Wistar,
pubmed-meshheading:17883399-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:17883399-Tumor Necrosis Factor-alpha
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| pubmed:year |
2007
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| pubmed:articleTitle |
Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute-phase response.
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| pubmed:affiliation |
Experimental Neuropathology, Department of Pharmacology, University of Oxford, Oxford, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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