Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the hypothalamus following an immunological stressor

D M Kerr, N N Burke, G K Ford, T J Connor, B Harhen, L J Egan, D P Finn, M Roche

Research output: Contribution to journalArticle (Academic Journal)peer-review

45 Citations (Scopus)

Abstract

The endocannabinoid system is an important regulator of the nervous, neuroendocrine, and immune systems, thus representing a novel therapeutic target for stress-related neuroinflammatory and psychiatric disorders. However, there is a paucity of data relating to the effects of endocannabinoids on neuroinflammatory mediators following an immune stress/challenge in vivo. This study investigated the effects of URB597, a selective inhibitor of fatty acid amide hydrolyase (FAAH), the enzyme that preferentially metabolizes anandamide, on lipopolysaccharide (LPS)-induced increases in the expression of immune mediators in the hypothalamus. Systemic administration of URB597 increased the levels of anandamide and the related N-acylethanolamines, N-palmitoylethanolamide, and N-oleoylethanolamide, but not 2-arachidonoyl glycerol, in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in interleukin (IL)-1β expression while concurrently augmenting the LPS-induced increase in suppressor of cytokine signalling (SOCS)-3 expression. In addition, URB597 tended to enhance and reduce the LPS-induced increase in IL-6 and IL-10 mRNA expression, respectively. LPS-induced increases in peripheral cytokine levels or plasma corticosterone were not altered by URB597. The present study provides evidence for a role for FAAH in the regulation of LPS-induced expression of inflammatory mediators in the hypothalamus. Improved understanding of endocannabinoid-mediated regulation of neuroimmune function has fundamental physiological and potential therapeutic significance in the context of stress-related disorders.
Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalNeuroscience
Volume204
DOIs
Publication statusPublished - 1 Mar 2012

Bibliographical note

Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Keywords

  • Animals
  • Benzamides
  • Cannabinoid Receptor Modulators
  • Carbamates
  • Cytokines
  • Endocannabinoids
  • Hypothalamus
  • Inflammation Mediators
  • Lipopolysaccharides
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological

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