title: Tumor necrosis factor involvement in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated endotoxin hypersensitivity in C57BL/6J mice congenic at the Ah locus.
abstract: An experimental model of endotoxin-induced release of tumor necrosis factor-alpha (TNF) into the serum of C57BL/6J mice congenic at the Ah locus was used to investigate the effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on TNF production. TCDD exposure of Ah-responsive mice (Ahbb) resulted in a dose-dependent increase in the concentration of TNF in the serum of endotoxin-exposed mice, with a significant increase observed at a dose of 10 micrograms/kg TCDD. At a dose of 500 micrograms/kg TCDD, Ahbb mice demonstrated a 46-fold increase in serum TNF levels compared to control. In contrast, congenic Ah-receptor deficient mice (Ahdd) did not show a significant increase in serum TNF levels until exposed to 150 micrograms/kg TCDD, and the maximum response was an 8-fold increase over control. These data suggest that increased TNF production may be responsible for endotoxin hypersensitivity in TCDD-treated mice and that the Ah locus mediates this response.
authors.affiliation: Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: G C
authors.initials: GC
authors.lastname: Clark
authors.forename: M J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: A M
authors.initials: AM
authors.lastname: Tritscher
authors.forename: G W
authors.initials: GW
authors.lastname: Lucier
mesh_terms: D000483:Alleles; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics*; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D004731:Endotoxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D014409:Tumor Necrosis Factor-alpha