urb-597 and Encephalitis

The present study examined the effect of enhancing fatty acid amide hydrolase (FAAH) substrate levels in vivo on Toll-like receptor (TLR)3-induced neuroinflammation. Systemic and central (i.c.v.) administration of the FAAH inhibitor URB597 increased hippocampal levels of the N-acylethanolamines palmitoylethanolamide and oleoylethanolamide, but not anandamide. Systemic URB597 increased IFNα, IFNγ and IL-6 expression following TLR3 activation and attenuated TLR3-induced IL-1β and TNFα expression. In comparison, central URB597 administration attenuated the TLR3-induced increase in TNFα and IFNγ expression (and associated downstream genes IP-10 and SOCS1), while concurrently increasing IL-10 expression. These data support an important role for FAAH-mediated regulation of TLR3-induced neuroinflammatory responses.

Topics: Amidohydrolases; Animals; Benzamides; Carbamates; Chromatography, Liquid; Cytokines; Drug Administration Routes; Encephalitis; Enzyme Inhibitors; Gene Expression Regulation; Hippocampus; Interferon Inducers; Male; Poly I-C; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tandem Mass Spectrometry; Toll-Like Receptor 3