Enhancement of antifungal chemotherapy by interferon-gamma in experimental systemic cryptococcosis.
The possible enhancement, using immunotherapy with interferon-gamma (IFN-gamma), combined with conventional antifungal therapy, was studied in a murine model of systemic cryptococcosis. Four weeks after intravenous challenge, infection was quantified in brains and livers of survivors. Groups received IFN-gamma every other day beginning 7 days before (prophylaxis), or after infection (14 doses), or amphotericin B post-infection, or combinations of these regimens. IFN-gamma alone was modestly effective, but impressively and significantly potentiated amphotericin in reducing infection in the most important site of infection, the brain. The efficacy was seen after lethal and non-lethal challenges, and when IFN-gamma was given by the intravenous or subcutaneous routes. In non-lethal infection, only the combination amphotericin-IFN-gamma resulted in sterilization of the central nervous system. Potentiation of fluconazole was less impressive. Adding prophylactic IFN-gamma doses to IFN-gamma therapy did not consistently enhance the therapeutic effect. These results suggest IFN-gamma may have a role in potentiating conventional antifungal therapy of cryptococcosis.
Lutz
J E
JE
Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, San Jose, California 95128-2699, USA.
Clemons
K V
KV
Stevens
D A
DA
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000302:isolation & purification*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000935:Antifungal Agents; D000666:Amphotericin B; D007371:Interferon-gamma; D015725:Fluconazole