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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1997-1-6
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pubmed:abstractText |
1. The role of tumour necrosis factor-alpha (TNF-alpha) in fever is controversial. Some studies have indicated that TNF-alpha acts as a cryogen to inhibit fever, while others suggest that TNF-alpha is an endogenous pyrogen which mediates fever. The majority of studies in experimental animals supporting a cryogenic action have been conducted using human (h)TNF-alpha, which has been shown to bind only to one (p55) of the two TNF-alpha receptors in rodents. 2. The aim of the present investigation was to study the role of TNF-alpha in fever by comparing effects of hTNF-alpha, which binds only to the p55 receptor, with those of murine (m) TNF-alpha, which binds to both p55 and p75 TNF-alpha receptors, and to investigate the relationship between TNF-alpha and interleukin-1 (IL-1), an important endogenous pyrogen. 3. Injection of hTNF-alpha (0.3-10 micrograms kg-1, i.p.) had no effect on core temperature in conscious rats (measured by remote radiotelemetry), whereas mTNF-alpha (3 micrograms kg-1) induced fever which was maximal 1 h after the injection (38.2 +/- 0.2 degrees C compared to 37.3 +/- 0.1 degrees C in controls). Intracerebroventricular (i.c.v.) administration of either form of TNF-alpha elicited dose-dependent fever at doses higher than 0.12 microgram kg-1. 4. Peripheral injection of hIL-1 beta (1 microgram kg-1) resulted in fever (38.3 +/- 0.2 degree C compared to 37.2 +/- 0.1 degrees C in controls at 2 h), which was significantly attenuated (P < 0.01) by co-administration of a sub-pyrogenic dose of hTNF-alpha (1 microgram kg-1), but was unaffected by co-administration of mTNF-alpha (0.1 or 0.3 microgram kg-1, i.p.). In contrast, intracerebroventricular (i.c.v.) co-administration of a sub-pyrogenic dose (0.12 microgram kg-1) of hTNF-alpha did not attenuate fever induced by intraperitoneal (i.p.) injection of IL-1 beta, and sub-pyrogenic dose (0.12 microgram kg-1, i.c.v.) of mTNF-alpha significantly prolonged the febrile response to IL-1 beta. Pretreatment of animals with anti-TNF-alpha antiserum (i.c.v.) did not affect the febrile response to systemic IL-1 beta. 5. Animals injected i.p. with a pyrogenic dose of mTNF-alpha developed fever (38.2 +/- 0.2 degrees C compared to 37.3 +/- 0.1 degrees C in controls 2 h after the injection) that was completely abolished by peripheral administration of IL-1ra (2 mg kg-1, P < 0.001), while i.c.v. administration of IL-1ra (400 micrograms/rat) did not affect mTNF-alpha-induced fever. 6. These data indicate that endogenous TNF-alpha is probably a pyrogen and that previous results suggesting cryogenic actions of TNF-alpha resulted from the use of a heterologous protein in the rat. The markedly contrasting effects of mTNF-alpha and TNF-alpha could result from different interactions with the two TNF-alpha receptor subtypes. The data also suggest that fever induced by exogenous TNF-alpha is mediated via release of IL-1 beta in peripheral tissues, but not in the brain.
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pubmed:grant | |
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1320461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1322675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1409612,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1443236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1849278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-1986393,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2151767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2221137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2295861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2309925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2316707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2316725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2456628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2492162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-2918329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-3162987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-3260533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-3263887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-3447641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-3486936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-7754524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-7810749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-7990930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-8072858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-8084523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-8168971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-8214140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8864524-8255404
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0007-1188
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1919-24
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8864524-Animals,
pubmed-meshheading:8864524-Body Temperature,
pubmed-meshheading:8864524-Drug Interactions,
pubmed-meshheading:8864524-Fever,
pubmed-meshheading:8864524-Humans,
pubmed-meshheading:8864524-Interleukin-1,
pubmed-meshheading:8864524-Male,
pubmed-meshheading:8864524-Rats,
pubmed-meshheading:8864524-Rats, Sprague-Dawley,
pubmed-meshheading:8864524-Tumor Necrosis Factor-alpha
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pubmed:year |
1996
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pubmed:articleTitle |
The role of TNF-alpha in fever: opposing actions of human and murine TNF-alpha and interactions with IL-beta in the rat.
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pubmed:affiliation |
School of Biological Sciences, Manchester, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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