title: C3H/HeJ mice are refractory to lipopolysaccharide in the brain.
abstract: C3H/HeJ mice are refractory to lipolysaccharide (LPS) in the periphery, primarily because their macrophages do not respond to LPS and produce pro-inflammatory cytokines such as interleukin-1 (IL-1). To determine if they are also refractory to LPS in the brain, behavior of C3H/HeJ mice was compared to LPS-sensitive C3H/HeOuJ mice following intracerebroventricular (I.C.V.) injection of LPS. Whereas ICV injection of LPS (3-1000 ng/mouse) depressed social behavior, food motivation, object investigation and body weight in C3H/HeOuJ mice, C3H/HeJ mice were entirely refractory to LPS in the brain. To determine if the refractoriness of C3H/HeJ mice could result from an inability to synthesize IL-1, recombinant murine IL-1 was injected I.C.V. in both mouse strains. Central administration of IL-1 (1 or 2 ng/mouse) depressed social behavior and body weight similarly in both endotoxin-sensitive C3H/HeOuJ mice and endotoxin-resistant C3H/HeJ mice. That C3H/HeJ mice were refractory to the behavioral effects of central LPS, but not IL-1, suggests that microglia (and other cells in the brain) in C3H/HeJ mice have in common with peripheral macrophages, an inability to respond to LPS and produce cytokines. These data suggest a genetic basis for sickness behavior and demonstrate the utility of preventing central cytokine production in manipulating LPS-induced sickness behavior.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Johnson
authors.forename: G
authors.initials: G
authors.lastname: Gheusi
authors.forename: S
authors.initials: S
authors.lastname: Segreti
authors.forename: R
authors.initials: R
authors.lastname: Dantzer
authors.forename: K W
authors.initials: KW
authors.lastname: Kelley
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004351:Drug Resistance / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D006824:Hybridization, Genetic; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics / Q000502:physiology*; D008815:Mice, Inbred Strains / Q000235:genetics; D012919:Social Behavior
chemical_list: D008070:Lipopolysaccharides