Source:http://linkedlifedata.com/resource/pubmed/id/16809483
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2006-10-9
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| pubmed:abstractText |
Interleukin (IL)-6 is an important humoral mediator of fever following infection and inflammation and satisfies a number of criteria for a circulating pyrogen. However, evidence supporting such a role is diminished by the moderate or even absent ability of the recombinant protein to induce fever and activate the cyclooxygenase-2 (COX-2) pathway in the brain, a prerequisite step in the initiation and maintenance of fever. In the present study, we investigated the role of endogenous circulating IL-6 in a rodent model of localized inflammation, by neutralizing its action using a specific antiserum (IL-6AS). Rats were injected with LPS (100 microg/kg) or saline into a preformed air pouch in combination with an intraperitoneal injection of either normal sheep serum or IL-6AS (1.8 ml/rat). LPS induced a febrile response, which was accompanied by a significant rise in plasma IL-6 and nuclear STAT3 translocation in endothelial cells throughout the brain 2 h after treatment, including areas surrounding the sensory circumventricular organs and the median preoptic area (MnPO), important regions in mediating fever. These responses were abolished in the presence of the IL-6AS, which also significantly inhibited the LPS-induced upregulation of mRNA expression or immunoreactivity (IR) of the inducible form of COX, the rate-limiting enzyme for PGE2-synthesis. Interestingly, nuclear signal transducer and activator of transcription (STAT)3-positive cells colocalized with COX-2-IR, signifying that IL-6-activated cells are directly involved in PGE2 production. These observations suggest that IL-6 is an important circulating pyrogen that activates the COX-2-pathway in cerebral microvasculature, most likely through a STAT3-dependent pathway.
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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/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrogens,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0363-6119
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
291
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
R1316-26
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| pubmed:meshHeading |
pubmed-meshheading:16809483-Animals,
pubmed-meshheading:16809483-Body Temperature,
pubmed-meshheading:16809483-Brain,
pubmed-meshheading:16809483-Cyclooxygenase 2,
pubmed-meshheading:16809483-Endothelial Cells,
pubmed-meshheading:16809483-Fever,
pubmed-meshheading:16809483-Gene Expression Regulation,
pubmed-meshheading:16809483-Immune Sera,
pubmed-meshheading:16809483-Interleukin-6,
pubmed-meshheading:16809483-Lipopolysaccharides,
pubmed-meshheading:16809483-Male,
pubmed-meshheading:16809483-NF-kappa B,
pubmed-meshheading:16809483-Pyrogens,
pubmed-meshheading:16809483-RNA, Messenger,
pubmed-meshheading:16809483-Rats,
pubmed-meshheading:16809483-Rats, Sprague-Dawley,
pubmed-meshheading:16809483-STAT3 Transcription Factor,
pubmed-meshheading:16809483-Suppressor of Cytokine Signaling Proteins
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| pubmed:year |
2006
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| pubmed:articleTitle |
Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain.
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| pubmed:affiliation |
Douglas Hospital Research Centre, Dept. of Psychiatry, McGill Univ., 6875 Blvd. LaSalle, Verdun, Montreal, QC, H4H 1R3, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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