Role of endogenous endotoxin on tumor necrosis factor-hypersensitivity caused by D-galactosamine challenge.
We examined the role of endotoxin in the mechanism of recombinant human tumor necrosis factor (rhTNF)-hypersensitivity caused by D-galactosamine (GalN). We used polymyxin B, an antibiotic with anti-endotoxin activity, to determine the participation of endogenous endotoxin. The glycogen and blood glucose level of rhTNF (1 x 10(4) units/mouse, i.v.)-injected mice was lower at 7 h post-intoxication than that in the control. Administration of rhTNF to GalN (700 mg/kg, i.p.)-treated mice resulted in lower levels of glycogen and blood glucose than those in animals treated with rhTNF alone. In mice pretreated with polymxin B (20 mg/kg, i.p.), the level at 7 h after rhTNF/GalN-injection was markedly increased compared to that in mice treated with rhTNF/GalN alone. The injection of a low endotoxin dose (0.1 mg/kg, i.p.) markedly decreased the rectal temperature in mice treated with rhTNF (5 x 10(3) units/mouse, i.v.) and GalN, and none of these animals survived after treatment for 18 h. These findings suggest that endogenously produced endotoxin may contribute to the extent of rhTNF-hypersensitivity caused by GalN.
Sakaguchi
S
S
First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, Sendai, Japan.
Furusawa
S
S
Yokota
K
K
Sasaki
K
K
Takayanagi
M
M
Takayanagi
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D005688:Galactosamine / Q000008:administration & dosage*; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D011112:Polymyxin B / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology; D012007:Rectum; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology*
D001786:Blood Glucose; D004731:Endotoxins; D008112:Liver Glycogen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D011112:Polymyxin B