Linked Life Data

16024732

Source:http://linkedlifedata.com/resource/pubmed/id/16024732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-10-20
pubmed:abstractText
Interleukin-12 (IL-12) is an inflammatory Th1-driving cytokine that has been clinically used as immune therapy and vaccine adjuvant. Recently, it was reported that patients receiving IL-12 presented hyperalgesia. In the present study, we investigated the mechanical hyperalgesic effect of IL-12 in rats using two tests: 1) paw constant pressure and 2) electronic pressure-meter. In both tests, intraplantar administration of IL-12 (3-30 ng paw(-1)) caused a dose- and time-dependent mechanical hyperalgesia, which peaked between 3 to 5 h, remaining significantly different from control levels until 7 h and resolved 24 h postinjection. However, the same doses of IL-12 did not induce thermal hyperalgesia, determined using the Hargreaves test. Pretreatments with effective doses of indomethacin (2.5 mg kg(-1)), atenolol (1 mg kg(-1)), 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethylpropanoic acid, sodium (MK886) (5-lipoxygenase activating protein inhibitor; 1 mg kg(-1)), or cyclo[(D)Trp-(D)Asp-Pro-(D)Val-Leu] (BQ123) [endothelin (ET)(A) receptor antagonist; 30 nmol paw(-1)] did not inhibit IL-12-evoked mechanical hyperalgesia (10 ng paw(-1)). However, dexamethasone (2 mg kg(-1)), morphine (3-12 microg paw(-1)), and N-cys-2,6 dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarboyl-d-norleucine (BQ788) (ET(B) receptor antagonist; 3-30 nmol paw(-1)) did inhibit IL-12 hyperalgesia. Furthermore, neither pretreatment with effective doses of antiserum against rat-TNF-alpha (50 microl paw(-1)) nor against IL-18 (10 microg paw(-1)) inhibited the IL-12-induced hyperalgesia. Likewise, antiserum against IL-12 (10 ng paw(-1)) did not alter IL-18-induced hyperalgesia. In conclusion, we demonstrated for the first time that IL-12 is a prohyperalgesic cytokine that induces mechanical hyperalgesia mediated by endothelin action on the ET(B) receptor. Therefore, endothelin receptor antagonism could be beneficial in controlling IL-12 therapy-induced pain or hyperalgesia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16024732-Analgesics, pubmed-meshheading:16024732-Analgesics, Opioid, pubmed-meshheading:16024732-Animals, pubmed-meshheading:16024732-Anti-Inflammatory Agents, pubmed-meshheading:16024732-Antibodies, Blocking, pubmed-meshheading:16024732-Cytokines, pubmed-meshheading:16024732-Dose-Response Relationship, Drug, pubmed-meshheading:16024732-Eicosanoids, pubmed-meshheading:16024732-Endothelins, pubmed-meshheading:16024732-Foot, pubmed-meshheading:16024732-Hot Temperature, pubmed-meshheading:16024732-Hyperalgesia, pubmed-meshheading:16024732-Injections, Subcutaneous, pubmed-meshheading:16024732-Interleukin-12, pubmed-meshheading:16024732-Male, pubmed-meshheading:16024732-Morphine, pubmed-meshheading:16024732-Pain, pubmed-meshheading:16024732-Pain Measurement, pubmed-meshheading:16024732-Physical Stimulation, pubmed-meshheading:16024732-Rats, pubmed-meshheading:16024732-Rats, Wistar, pubmed-meshheading:16024732-Receptor, Endothelin A, pubmed-meshheading:16024732-Receptor, Endothelin B, pubmed-meshheading:16024732-Sympathetic Nervous System
pubmed:year
2005
pubmed:articleTitle
Nociceptive effect of subcutaneously injected interleukin-12 is mediated by endothelin (ET) acting on ETB receptors in rats.
pubmed:affiliation
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't