Tolerance against tumor necrosis factor alpha (TNF)-induced hepatotoxicity in mice: the role of nitric oxide.
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.
Bohlinger
I
I
Faculty of Biology, University of Konstanz, Germany.
Leist
M
M
Barsig
J
J
Uhlig
S
S
Tiegs
G
G
Wendel
A
A
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*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase