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 C ryptococcus neoformans infection in C57BL/6 mice exposed to LP-BM5 murine l eukaemia virus (MuLV) (MAIDS mice) was investigated. Mice were infected int ratracheally 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 infec ted mice was determined. Lanoconazole and fluconazole had a similar inhibit ory 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 br ains 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, where as fluconazole did not. A predominance of type 2 T-cell responses was demon strated 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 th ey were stimulated with an anti-CD3 monoclonal antibody. These results sugg est that lanoconazole may have the potential to inhibit the growth of C. ne oformans in AIDS patients with a predominance of type 2 T-cell responses.