Suzuki F, Furukawa K, Sasaki H, Pollard RB; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 29 (abstract no. 11235).
University of Texas Medical Branch, Galveston, USA.
OBJECTIVE: C. neoformans, a common opportunistic fungal pathogen, has been shown as a serious pathogenic organism in patients with AIDS. Even with aggressive chemotherapy, the high mortality rates of AIDS patients infected with C. neoformans have persisted. In the present study, the effects of a new antifungal drug, lanoconazole, on the infection of C. neoformans in MAIDS mice were investigated. METHODS: MAIDS mice (C57BL/6 mice infected with 4.5 x 10(2) PFU/mouse of LP-BM5 MuLV), 50 days after infection were exposed intratracheally to C. neoformans, strain 613D. These mice were treated with a 10 mg/kg oral dose of lanoconazole (Tsumura Co., Tokyo, Japan), or fluconazole (a positive control) once daily for 30 days beginning 1 day after the fungal infection. Antifungal effects of the two compounds were determined by the reduction in numbers of C. neoformans cells in lungs and brains of infected mice. Type 2 T cell responses were determined as a titer of IL-4 and IL-10 in culture fluids of splenic cells derived from infected MAIDS mice. Cytokines produced by anti-CD3 mAb stimulated splenic cells were determined by ELISA. RESULTS: The growth of C. neoformans in brains was equally inhibited in normal mice after treatment with lanoconazole or fluconazole. However, in MAIDS mice, inhibitory efficiencies of lanoconazole on the fungal growth was greater than that of fluconazole. The inhibitory effect of fluconazole on fungal growth was reduced in normal mice treated with a mixture of type 2 cytokines. However, the antifungal effect of lanoconazole showed no reduction in normal mice treated with a type 2 cytokine mixture. CONCLUSIONS: The growth of C. neoformans was inhibited in MAIDS mice treated with lanoconazole. The antifungal activity of fluconazole was influenced by type 2 cytokines, whereas no inhibition was seen in lanoconazole activity. These results may suggest the potential of lanoconazole in AIDS patients infected with C. neoformans.
Publication Types:
Keywords:
- Animals
- Antibodies, Monoclonal
- Antifungal Agents
- Cryptococcosis
- Cytokines
- Fluconazole
- Humans
- Imidazoles
- Interleukin-10
- Interleukin-4
- Japan
- Mice
- Mice, Inbred C57BL
- Miconazole
- Spleen
- T-Lymphocytes
- Tokyo
- latoconazole
- visilizumab
Other ID:
UI: 102226790
From Meeting Abstracts