title: Tolerance against tumor necrosis factor alpha (TNF)-induced hepatotoxicity in mice: the role of nitric oxide.
abstract: D-Galactosamine-sensitized mice challenged with tumor necrosis factor alpha (TNF) developed severe apoptotic and secondary necrotic liver injury as assessed by histology, measurement of cytosolic DNA fragments and determination of liver-specific enzymes in plasma. Pretreatment of mice with interleukin-1 beta (IL-1) resulted in elevated levels of nitrite/nitrate in serum and rendered mice insensitive towards TNF toxicity. Pharmacological doses of the nitric oxide (NO) donor sodium nitroprusside (SNP) also conferred complete protection against TNF toxicity, suggesting a possible link between IL-1- and NO-induced protection. However, NO-synthesis inhibition by NG-monomethyl-L-arginine failed to abrogate IL-1-induced tolerance against TNF toxicity. We conclude that IL-1 and NO protect against TNF-induced liver injury through distinct pathways.
authors.affiliation: Faculty of Biology, University of Konstanz, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bohlinger
authors.forename: M
authors.initials: M
authors.lastname: Leist
authors.forename: J
authors.initials: J
authors.lastname: Barsig
authors.forename: S
authors.initials: S
authors.lastname: Uhlig
authors.forename: G
authors.initials: G
authors.lastname: Tiegs
authors.forename: A
authors.initials: A
authors.lastname: Wendel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase