THERAPEUTIC EFFECT OF INTERFERON-GAMMA GENE-TRANSFER IN EXPERIMENTAL VISCERAL LEISHMANIASIS

Interferon (IFN)-gamma, in both natural endogenous form and administer ed as exogenous protein, induces control over visceral Leishmania dono vani in experimentally infected BALB/c mice. To further characterize t he therapeutic role of IFN-gamma in host defense against intracellular L. donovani, the efficacy of IFN-gamma delivered by gene transfer was tested. One week after infection, normal and IFN-gamma gene-disrupted (GKO) BALB/c mice were injected with an IFN-gamma gene-bearing mammal ian expression plasmid (pIFN). Plasmid-specific IFN-gamma transcripts were detected in liver and spleen. Whereas liver parasite burdens more than doubled in untreated and mock-treated normal and GKO mice during the subsequent 2 weeks, animals injected with pIFN had controlled vis ceral infection and reduced parasite burdens. These results indicate t hat, in infected tissues, IFN-gamma delivered by gene transfer enhance s control over disseminated intracellular infection.