ARAN - Access to Research at NUI Galway

Augmentation of endogenous cannabinoid tone modulates lipopolysaccharide-induced alterations in circulating cytokine levels in rats

ARAN - Access to Research at NUI Galway

Show simple item record

dc.contributor.author Roche, Michelle en
dc.contributor.author Kelly, John P. en
dc.contributor.author O'Driscoll, Maeve en
dc.contributor.author Finn, David P. en
dc.date.accessioned 2011-02-11T21:41:44Z en
dc.date.available 2011-02-11T21:41:44Z en
dc.date.issued 2008-10 en
dc.identifier.citation Roche, M., J. Kelly, et al. (2008). "Augmentation of endogenous cannabinoid tone modulates lipopolysaccharide-induced alterations in circulating cytokine levels in rats." Immunology 125(2): 263 - 71. en
dc.identifier.issn 1365-2567 en
dc.identifier.uri http://hdl.handle.net/10379/1614 en
dc.description.abstract The endogenous cannabinoid system plays an important role in regulating the immune system. Modulation of endogenous cannabinoids represents an attractive alternative for the treatment of inflammatory disorders. This study investigated the effects of URB597, a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme catalysing degradation of the endogenous cannabinoid anandamide, and AM404, an inhibitor of anandamide transport, on lipopolysaccharide (LPS)-induced increases in plasma cytokine levels in rats. Both URB597 and AM404 potentiated the LPS-induced increase in plasma tumour necrosis factor-¿ (TNF-¿) levels. The peroxisome proliferator-activated receptor ¿ (PPAR¿) antagonist, GW9662, attenuated the AM404-induced augmentation of TNF-¿ levels. Furthermore, the selective cannabinoid CB1 and CB2 receptor antagonists, AM251 and AM630 respectively, and the transient receptor potential vanilloid receptor-1 (TRPV1) antagonist, SB366791, reduced LPS-induced TNF-¿ plasma levels both alone and in combination with AM404. In contrast, AM404 inhibited LPS-induced increases in circulating interleukin-1¿ (IL-1¿) and IL-6. AM251 attenuated the immunosuppressive effect of AM404 on IL-1¿. None of the antagonists altered the effect of AM404 on LPS-induced IL-6. Moreover, AM251, AM630 and SB366791, administered alone, inhibited LPS-induced increases in plasma IL-1¿ and IL-6 levels. In conclusion, inhibition of endocannabinoid degradation or transport in vivo potentiates LPS-induced increases in circulating TNF-¿ levels, an effect which may be mediated by PPAR¿ and is also reduced by pharmacological blockade of CB1, CB2 and TRPV1. The immunosuppressive effect of AM404 on IL-1¿ levels is mediated by the cannabinoid CB1 receptor. Improved understanding of endocannabinoid-mediated regulation of immune function has fundamental physiological and potential therapeutic significance. en
dc.format application/pdf en
dc.language.iso en en
dc.publisher Blackwell en
dc.subject Anandamide en
dc.subject Interleukin-1 en
dc.subject Interleukin-6 en
dc.subject Rodent en
dc.subject Tumour necrosis factor en
dc.subject National Centre for Biomedical Engineering Science en
dc.title Augmentation of endogenous cannabinoid tone modulates lipopolysaccharide-induced alterations in circulating cytokine levels in rats en
dc.type Article en
dc.local.publishedsource http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561133 en
dc.description.peer-reviewed peer-reviewed en
dc.contributor.funder Irish Health Research Board en

Files in this item

This item appears in the following Collection(s)

Show simple item record