Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 2
pubmed:dateCreated
1997-10-23
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R873-9
pubmed:dateRevised
2007-11-15
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
pubmed:year
1997
pubmed:articleTitle
Attenuation of lipopolysaccharide fever in rats by protein kinase C inhibitors.
pubmed:affiliation
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.