Role of Endogenous Endotoxin on Tumor Necrosis Factor-Hypersensitivity Caused by D-Galactosamine Challenge

• Published in: Biological & pharmaceutical bulletin Vol. 23; no. 1; pp. 116 - 118
• Main Authors: SAKAGUCHI, Shuhei, FURUSAWA, Shinobu, YOKOTA, Katsushi, SASAKI, Ken-ichi, TAKAYANAGI, Motoaki, TAKAYANAGI, Yoshio
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.2000; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Temperature - drug effects; endotoxin; Endotoxins - toxicity; galactosamine; Galactosamine - administration & dosage; Hypersensitivity - etiology; Hypersensitivity - immunology; hypersensivity; Liver Glycogen - metabolism; Male; Medical sciences; Mice; Pharmacology. Drug treatments; polymyxin B; Polymyxin B - pharmacology; Recombinant Proteins - immunology; Rectum; tumor necrosis factor; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - immunology; Galactosamine; Intraperitoneal administration; Intravenous administration; Glycogen; Cyclic peptides; Hypersensitivity; Body temperature; Rodentia; Cytokine; Glucose; Endotoxin; Polymyxin B; Vertebrata; Antibiotic; Mammalia; Mouse; Tumor necrosis factor; Polypeptide; Animal; Recombinant protein; Antibacterial agent
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.23.116

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 (1×104 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 (5×103 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.