Effect of Continuous Administration of Interferon- in Experimental Visceral Leishmaniasis

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Abstract
In experimental visceral leishmaniasis, intermittently administered Interferon-γ (IFN-γ) induces antileishmanial activity, which is primarily microbistatic. To determine if the efficacy of IFN-γ immunotherapy could be enhanced by continuous delivery, Leishmania donovani-infected mice were treated using a subcutaneous osmotic pump. Once-daily intraperitoneal injections of 105 or 106 units of IFN-γ inhibited the replication of L. donovani within liver macrophages but overall did not reduce liver parasite burdens. In contrast, a comparable dose of IFN-γ (2.4 × 105 units/day) administered continuously induced an enhanced effect and reduced liver burdens by almost 50%. Although pump delivery did not similarly increase the efficacy of antimony chemotherapy in infected mice, continuous treatment with IFN-γ plus antimony produced an additive antileishmanial effect.These results suggest that continuous infusions ofmacrophage-activating lymphokines such as IFN-γ (used alone or in combination with chemotherapy) may be required to optimize in vivo antimicrobial effects.