Therapeutic effect of interferon-gamma gene transfer in experimental visceral leishmaniasis.

Interferon (IFN)-gamma, in both natural endogenous form and administered as exogenous protein, induces control over visceral Leishmania donovani in experimentally infected BALB/c mice. To further characterize the 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 mammalian 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 visceral infection and reduced parasite burden. These results indicate that, in infected tissues, IFN-gamma delivered by gene transfer enhances control over disseminated intracellular infection.