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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3 Pt 2
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pubmed:dateCreated |
1997-10-23
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pubmed:abstractText |
The purpose of this study was to assess the effects of inhibitors of protein kinase C (PKC) on lipopolysaccharide (LPS)-induced fever and changes in circulating interleukin-6 (IL-6) levels in freely moving biotelemetered rats. We used PKC inhibitors with different inhibition constants (Ki): H-7 (Ki = 6 microM) and chelerythrine (Chel; Ki = 0.66 microM; a more potent PKC inhibitor). Rats were injected subcutaneously with either 3 or 15 microM/kg of these inhibitors and then 1 h later were injected intraperitoneally with LPS (50 micrograms/kg). Blood samples for IL-6 bioassay were collected 4 h after LPS injection. H-7 at lower doses did not significantly affect fever and LPS-induced elevation of circulating IL-6, whereas at a higher dose (15 microM/kg) H-7 reduced both fever and the increase of IL-6 (analysis of variance, Scheffé's test, P < 0.05). Chel (3 and 15 microM/kg) significantly reduced fever and almost completely inhibited the LPS-induced elevation of plasma IL-6. In separate experiments, we studied the effect of H-7 on antipyresis due to dexamethasone (Dex). Dex at a dose of 0.6 microM/kg given subcutaneously 1 h before LPS partially prevented fever (approximately 55% inhibition) and attenuated the increase of IL-6 (P < 0.05). Simultaneous pretreatment of the rats with Dex and H-7 (3 microM/kg; a dose that did not affect fever and IL-6 elevation) led to a potentiation of the antipyretic effect of Dex, resulting in no fever. H-7 did not potentiate, however, the inhibitory effect of Dex on LPS-induced elevation of circulating IL-6. We conclude that PKC is involved in the regulation of LPS fever and constitutes a rate-limiting factor in modulation of the fever by glucocorticoids.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, Non-Narcotic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzophenanthridines,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Phenanthridines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/chelerythrine
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R873-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9321862-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:9321862-Alkaloids,
pubmed-meshheading:9321862-Analgesics, Non-Narcotic,
pubmed-meshheading:9321862-Analysis of Variance,
pubmed-meshheading:9321862-Animals,
pubmed-meshheading:9321862-Benzophenanthridines,
pubmed-meshheading:9321862-Body Temperature Regulation,
pubmed-meshheading:9321862-Dexamethasone,
pubmed-meshheading:9321862-Enzyme Inhibitors,
pubmed-meshheading:9321862-Escherichia coli,
pubmed-meshheading:9321862-Fever,
pubmed-meshheading:9321862-Interleukin-6,
pubmed-meshheading:9321862-Lipopolysaccharides,
pubmed-meshheading:9321862-Male,
pubmed-meshheading:9321862-Phenanthridines,
pubmed-meshheading:9321862-Protein Kinase C,
pubmed-meshheading:9321862-Rats,
pubmed-meshheading:9321862-Rats, Sprague-Dawley,
pubmed-meshheading:9321862-Time Factors
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pubmed:year |
1997
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pubmed:articleTitle |
Attenuation of lipopolysaccharide fever in rats by protein kinase C inhibitors.
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pubmed:affiliation |
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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