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.
Taylor
A P
AP
Department of Medicine, Cornell University Medical College, New York, New York, USA.
Murray
H W
HW
D000818:Animals; D002460:Cell Line; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger; D014162:Transfection
D012333:RNA, Messenger; D007371:Interferon-gamma