title: Non-specific resistance induced by a low-toxic lipid A analogue, DT-5461, in murine salmonellosis.
abstract: The ability of DT-5461, a chemically synthetic low-toxic lipid A analogue, to activate anti-Salmonella activity in C3H/HeN mice was examined. Previous intraperitoneal (i.p.) injection of DT-5461 (100 micrograms or more/mouse) significantly hindered the bacterial growth in the peritoneal cavities of the mice after the i.p. infection with Salmonella typhimurium LT2 strain. The effect was the maximum when DT-5461 was given 6 h before the challenge. The injection of DT-5461 6 h in advance could also confer protection against the infection. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of recombinant murine IFN-gamma (10(3) U per mouse) and non-effective dose (10 micrograms) of DT-5461 together 6 h before the challenge. Bactericidal effect enhancement was seen in mice that had been injected with IFN-gamma at 6 h and DT-5461 at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order. The i.p. injection of DT-5461 recruits the exudate cells into the peritoneal cavities, and the phagocytic and bactericidal abilities of the macrophages in the exudate cells are apparently elevated. The mechanisms of non-specific resistance enhancement induced by DT-5461 were discussed.
authors.affiliation: Department of Microbiology, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Onozuka
authors.forename: S
authors.initials: S
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Yamasu
authors.forename: Y
authors.initials: Y
authors.lastname: Osada
authors.forename: M
authors.initials: M
authors.lastname: Nakano
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004187:Disaccharides / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000166:cytology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects; D012481:Salmonella Infections, Animal / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D004187:Disaccharides; D008050:Lipid A; C077208:DT 5461; D007371:Interferon-gamma