title: Pre-treatment of C57BL6/J mice with the TLR4 agonist monophosphoryl lipid A prevents LPS-induced sickness behaviors and elevations in dorsal hippocampus interleukin-1β, independent of interleukin-4 expression.
abstract: Peripheral administration of lipopolysaccharide (LPS) elevates production of pro-inflammatory cytokines, and motivates the expression of sickness behaviors. In this study, we tested the ability of an LPS-derived adjuvant, monophosphoryl lipid A (MPLA), to prevent LPS-induced sickness behaviors in a burrowing paradigm. Testing occurred over a three-day period. Animals received a single injection of either MPLA or saline the first two days of testing. On day three, animals received either LPS or saline. Tissue from the dorsal hippocampus was collected for qRT-PCR to assess expression of IL-1β and IL-4. Results indicate that, during the pre-treatment phase, administration of MPLA induces an immune response sufficient to trigger sickness behaviors. However, we observed that animals pre-treated with MPLA for two days were resistant to LPS-induced sickness behaviors on day three. Results from the qRT-PCR analysis indicated that LPS-treated animals pre-treated with MPLA expressed significantly less IL-1β compared to LPS-treated animals pre-treated with saline. However, we did not observe a significant difference in IL-4 expression between groups. Therefore, results indicate that under the given parameters of the study, MPLA pre-treatment protects against LPS-induced sickness behaviors, at least in part, by decreasing expression of the pro-inflammatory cytokine IL-1β.
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Eimerbrink
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kranjac
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: C
authors.initials: C
authors.lastname: St Laurent
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: White
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Weintraub
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pendry
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: R
authors.initials: R
authors.lastname: Madigan
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Hodges
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: L N
authors.initials: LN
authors.lastname: Sadler
authors.affiliation: Department of Biology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Chumley
authors.affiliation: Department of Psychology, Neurobiology of Aging Collaborative, Texas Christian University, Fort Worth, TX 76129, USA. Electronic address: g.boehm@tcu.edu.
authors.forename: G W
authors.initials: GW
authors.lastname: Boehm
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D055809:Illness Behavior / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D008050:Lipid A; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015847:Interleukin-4; C048436:monophosphoryl lipid A