title: Interleukin (IL)-12 deficiency in susceptible mice infected with Mycobacterium avium and amelioration of established infection by IL-12 replacement therapy.
abstract: Mycobacterium avium is an intracellular microorganism that infects and multiplies within macrophages. Cell-mediated immunity plays an important role in host defense, and interleukin (IL)-12, which is produced mainly by macrophages, is critical for its development. In a mouse model of disseminated M. avium infection, genetically susceptible BALB/c mice had increased mycobacterial growth and decreased IL-12 expression and developed large and numerous granulomas. In contrast, resistant DBA/2 mice exhibited reduced mycobacterial burden with increased IL-12 expression and developed fewer and smaller granulomas. In susceptible mice with established M. avium infection, IL-12 replacement therapy resulted in persistent reduction of mycobacterial burdens. IL-12 itself, however, could not inhibit mycobacterial growth in vitro. By enhancing host defenses, IL-12 exerts a potent mycobactericidal activity in vivo with low toxicity. This suggests that IL-12 replacement therapy is rational for M. avium infection in susceptible hosts.
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: J
authors.initials: J
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Kasama
authors.forename: T
authors.initials: T
authors.lastname: Katsura
authors.forename: K
authors.initials: K
authors.lastname: Kasahara
authors.forename: S F
authors.initials: SF
authors.lastname: Wolf
authors.forename: T
authors.initials: T
authors.lastname: Shimamura
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D018664:Interleukin-12 / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009162:Mycobacterium avium; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000033:anatomy & histology / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D018664:Interleukin-12