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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-9
pubmed:abstractText
Although peripherally released interleukin (IL)-6 is critical for fever, its role in sickness behaviors, in particular anorexia and lethargy, induced by lipopolysaccharide (LPS) administration appears to be less important. Using quantifiable measures of fever, anorexia and lethargy, that is, body temperature, food intake and voluntary wheel-running, we investigated whether the less-than-essential role for IL-6 in mediating sickness behaviors compared to fever implies important roles for other inflammatory mediators, particularly IL-1? and prostanoids, in these responses. Male Sprague-Dawley rats were randomly assigned to receive one of the following three injections before receiving a subcutaneous (SC) injection of LPS (250 ?g/kg) or saline: (1) intraperitoneal injection of pre-immune serum or antiserum to IL-6 (IL-6AS), to reduce the biological activity of peripherally released IL-6; (2) intracerebroventricular injection of vehicle or a caspase-1 inhibitor, to inhibit the production of mature IL-1?; or (3) intraperitoneal injection of vehicle or one of the two doses (1 or 10 mg/kg) of diclofenac, a nonselective cyclooxygenase inhibitor shown to block the formation of prostanoids. LPS administration induced fever, anorexia and lethargy with an accompanying increase in IL-6 and IL-1? concentrations in the circulation and IL-1? in the brain. Rats pre-treated with: (1) IL-6AS had reduced plasma levels of bioactive IL-6, no fever and attenuated sickness behaviors; (2) the caspase-1 inhibitor had reduced concentrations of IL-1? in the pre-frontal cortex, hypothalamus and hippocampus, and attenuated fever and sickness behaviors; (3) diclofenac had a dose-dependent attenuation in fever and sickness behaviors. Doses of diclofenac which completely abolished fever however had lesser effects on anorexia and lethargy. Our results confirm a difference in the sensitivity of sickness responses to IL-6 antagonism and identify that it may be related to different levels of sensitivity or responsiveness in brain regions and/or mechanisms, to prostanoids, IL-1?, or IL-6 itself.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-3360
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
608-22
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Differences in the relative involvement of peripherally released interleukin (IL)-6, brain IL-1? and prostanoids in mediating lipopolysaccharide-induced fever and sickness behavior.
pubmed:affiliation
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa. hardenlm@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't