Enhancement of antifungal chemotherapy by interferon-gamma in experimentalsystemic cryptococcosis

The possible enhancement, using immunotherapy with interferon-gamma (IFN-ga mma), combined with conventional antifungal therapy, was studied in a murin e model of systemic cryptococcosis. Four weeks after intravenous challenge, infection was quantified in brains and livers of survivors. Groups receive d 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 a nd 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 amph otericin-IFN-gamma resulted in sterilization of the central nervous system, Potentiation of fluconazole was less impressive. Adding prophylactic IFN-g amma doses to IFN-gamma therapy did not consistently enhance the therapeuti c effect. These results suggest IFN-gamma may have a role in potentiating c onventional antifungal therapy of cryptococcosis.