title: IL-1RA injected intra-cisterna magna confers extended prophylaxis against lipopolysaccharide-induced neuroinflammatory and sickness responses.
abstract: IL-1RA has been used intra-cerebrally to ameliorate neuroinflammatory responses. The present study explored the possibility that the bioactivity of IL-1RA administered intra-cerebrally may be prolonged in the CNS. hIL-1RA was detected in hippocampus from 2h to 14d post-ICM treatment. hIL-1RA ameliorated both the hippocampal cytokine (TNFα and NFκBIα) and sickness response to peripheral LPS administered 4d after hIL-1RA. Four days post treatment, hIL-1RA reduced the basal expression of IL-1R1, Iba-1, MHCII, and TLR4 and blunted the microglial IL-1β and IL-6 response to LPS ex vivo. IL-1RA might be administered prophylactically to prevent the neuroinflammatory effects of trauma.
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309-0345, USA. matt.frank@colorado.edu
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Frank
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Barrientos
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Thompson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weber
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002946:Cisterna Magna / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004660:Encephalitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides