title: [Profiles of expression of the therapeutic efficacy of KRM-1648 in mice infected with Mycobacterium avium complex at different challenge doses].
abstract: Studied were made on the profiles of the therapeutic efficacy of KRM-1648 (KRM) against Mycobacterium avium complex (MAC) infection, which was induced in mice at different challenge doses, in reducing bacterial growth in the visceral organs and altering the profiles of cytokine mRNA expression at the sites of infection. First, bacterial growth in the lungs of mice infected with either high or low challenge doses of MAC, was reduced due to KRM treatment. This effect was noted even in the early phase of infection (week 4) in mice, that were given a high-dose infection. Second, marked therapeutic efficacy of KRM was observed in mice, that were given low-dose MAC infection, in terms of the reduction in bacterial loads in the spleen. However, in mice given a high-dose bacterial challenge, KRM did not exhibit such an efficacy. Third, the expression of both proinflammatory cytokines (TNF-alpha, IFN-gamma) and anti-inflammatory cytokines (IL-10, TGF-beta) in mRNA levels were increased at 4 weeks after infection. Notably, all of the cytokines tested for the mRNA expression levels were higher in mice given a low-dose MAC infection as compared to those in mice given a high-dose infection. KRM treatment increased the mRNA levels of these cytokines at week 4, while TGF-beta mRNA expression at week 8 was conversely decreased by KRM treatment. These findings suggest that the profiles of the therapeutic efficacy of KRM vary in mice given low- or high-dose MAC infection.
authors.affiliation: Department of Microbiology and Immunology, Shimane Medical University.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Ogasawara
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: C
authors.initials: C
authors.lastname: Sano
authors.forename: H
authors.initials: H
authors.lastname: Tomioka
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D051379:Mice; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012294:Rifamycins / Q000627:therapeutic use*
chemical_list: D000904:Antibiotics, Antitubercular; D016207:Cytokines; D012333:RNA, Messenger; D012294:Rifamycins; C068980:KRM 1648