Efficacy of Recombinant Gamma Interferon for Treatment of Systemic Cryptococcosis in SCID Mice

Abstract

ABSTRACT We have previously shown that gamma interferon (IFN-γ) is a useful adjunct to therapy of experimental systemic cryptococcosis in normal mice. To better emulate AIDS patients, SCID mice were infected intravenously with Cryptococcus neoformans . Mice received no therapy, 3 mg of amphotericin B (AmB) per kg of body weight, or 10 5 U of IFN-γ alone (prophylactically and therapeutically or only therapeutically) or with AmB. In the first experiment, >75% of the mice survived. Therapy with AmB alone was efficacious compared to no therapy in all organs. Both regimens of IFN-γ alone were efficacious in the brain and lungs, and the combination of AmB and IFN-γ showed significant synergy in the kidneys. AmB alone cured 40% of mice of infection, whereas the combination regimens cured >50% of the mice and 90% of the brain infections. In a second study, IFN-γ again proved efficacious alone, and when given with AmB its efficacy was improved. Therapeutic IFN-γ alone was effective only in the liver compared to no therapy, and the combination regimen, although highly effective, showed no significant synergy. In a third experiment, AmB alone or in combination with IFN-γ prolonged survival compared to no therapy or IFN-γ alone. The combination regimen showed significant synergy over AmB alone in the brain, liver, kidneys, and lungs. AmB alone cured no mice of infections in more than two organs, whereas AmB in combination with IFN-γ cured 55% of infections in three or more organs. These results indicate that IFN-γ has therapeutic efficacy in severely immunodeficient animals, especially in combination with AmB. Significant synergistic activity was noted in all organs except the spleen. Overall, IFN-γ has utility as an adjunctive therapy against systemic cryptococcosis in the severely immunocompromised host.