Lanoconazole, a new imidazole antimycotic compound, protects MAIDS mice against encephalitis caused by Cryptococcus neoformans.
The protective effect of a new antifungal compound, lanoconazole, against Cryptococcus neoformans infection in C57BL/6 mice exposed to LP-BM5 murine leukaemia virus (MuLV) (MAIDS mice) was investigated. Mice were infected intratracheally with C. neoformans, strain 613D, 40 days after infection with LP-BM5 MuLV. They were treated orally with various doses of lanoconazole or with fluconazole 10 mg/kg (a positive control) once daily beginning 1 day after the fungal infection and continuing until the end of the experimental period. The number of C. neoformans cells in the lungs and brains of infected mice was determined. Lanoconazole and fluconazole had a similar inhibitory effect on the growth of C. neoformans in the brains and lungs of normal mice. Whereas lanoconazole inhibited the growth of C. neoformans in the brains and lungs of MAIDS mice, the pathogen grew in the brains of MAIDS mice treated with fluconazole. Lanoconazole reduced the number of C. neoformans in the brains of normal mice treated with a type 2 cytokine mixture, whereas fluconazole did not. A predominance of type 2 T-cell responses was demonstrated in MAIDS mice. Splenic T cells from MAIDS mice, but not those from normal mice, released interleukins 4 and 10 into the culture medium when they were stimulated with an anti-CD3 monoclonal antibody. These results suggest that lanoconazole may have the potential to inhibit the growth of C. neoformans in AIDS patients with a predominance of type 2 T-cell responses.
Furukawa
K
K
The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Sasaki
H
H
Pollard
R B
RB
Suzuki
F
F
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000254:growth & development*; D016207:Cytokines / Q000096:biosynthesis / Q000627:therapeutic use; D004660:Encephalitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D015725:Fluconazole / Q000627:therapeutic use; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology
D000935:Antifungal Agents; D016207:Cytokines; D006571:Heterocyclic Compounds; D007093:Imidazoles; C072774:latoconazole; D015725:Fluconazole