[In vitro and in vivo activities of chemically synthesized lipid A-subunit analogue, JTP3309, against mycobacterial infections in mice and in mouse peritoneal macrophages].
JTP3309, a newly synthesized lipid A-subunit analogue, was examined for in vitro and in vivo antimycobacterial activities. Firstly, the effect of JTP3309 on the in vitro antimycobacterial activity of murine peritoneal macrophages (M phi s) was studied. When resident peritoneal M phi s from CBA mice which had phagocytosed Mycobacterium avium were treated with JTP3309 once from 0 hr to 24 hr after the initiation of M phi cultivation or three times from 0 hr to 24 hr, 48 hr to 72 hr and 96 hr to 120 hr of culture period, there was no increase in the anti-M. avium activity of the treated M phi s. On the other hand, the bacterial growth was slightly inhibited in peritoneal M phi s from mice which had been injected with JTP3309, in comparison with that seen in resident M phi s. Secondly, protective and therapeutic efficacies of JTP3309 against M. avium and M. fortuitum infections in mice were studied, based on the suppression of the bacterial growth in the visceral organs including the lungs, kidneys and spleen. BALB/c mice infected i.v. with M. avium were given JTP3309 i.v. at the doses of 10 and 20 micrograms/mouse according to the following protocols; protocol A, two injections 4 and 1 day(s) before the infection; protocol B, once daily at days 1, 3, 5, 12, 19, 26, 33, 40, 47 and 54 after the infection; protocol C, once daily at days 1, 8, 15, 22, 29, 36, 43 and 50 after the infection. Only protocol A could reduce the number of CFU recovered from the spleen of infected mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Suzuki
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H
Japan Tobacco Inc. Central Phamaceutical Research Institute, Osaka.
Saito
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H
Sato
K
K
Tomioka
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H
D000818:Animals; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017737:Macrophages, Peritoneal / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009164:Mycobacterium Infections / Q000188:drug therapy*; D009162:Mycobacterium avium / Q000187:drug effects; D009170:Nontuberculous Mycobacteria / Q000187:drug effects
D007155:Immunologic Factors; C093653:JTP 3309; D008050:Lipid A