Journal of Antimicrobial Chemotherapy (2000) 46, 437-442
© 2000 The British Society for Antimicrobial Chemotherapy
Enhancement of antifungal chemotherapy by interferon-gamma in experimental systemic cryptococcosis
Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, San Jose, California and the Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
The possible enhancement, using immunotherapy with interferon-gamma (IFN-
), 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- every other day beginning 7 days before (prophylaxis), or after infection (14 doses), or amphotericin B post-infection, or combinations of these regimens. IFN- 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- was given by the intravenous or subcutaneous routes. In non-lethal infection, only the combination amphotericin–IFN- resulted in sterilization of the central nervous system. Potentiation of fluconazole was less impressive. Adding prophylactic IFN- doses to IFN- therapy did not consistently enhance the therapeutic effect. These results suggest IFN- may have a role in potentiating conventional antifungal therapy of cryptococcosis.
* Correspondence address. Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128-2699, USA. Tel: +1-408-885-4303; Fax: +1-408-885-4306; E-mail: stevens{at}leland.stanford.edu
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