Effect of continuous administration of interferon-gamma in experimental visceral leishmaniasis.
In experimental visceral leishmaniasis, intermittently administered interferon-gamma (IFN-gamma) induces antileishmanial activity, which is primarily microbistatic. To determine if the efficacy of IFN-gamma immunotherapy could be enhanced by continuous delivery, Leishmania donovani-infected mice were treated using a subcutaneous osmotic pump. Once-daily intraperitoneal injections of 10(5) or 10(6) units of IFN-gamma inhibited the replication of L. donovani within liver macrophages but overall did not reduce liver parasite burdens. In contrast, a comparable dose of IFN-gamma (2.4 x 10(5) 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-gamma plus antimony produced an additive antileishmanial effect. These results suggest that continuous infusions of macrophage-activating lymphokines such as IFN-gamma (used alone or in combination with chemotherapy) may be required to optimize in vivo antimicrobial effects.
Murray
H W
HW
Division of Infectious Diseases, Cornell University Medical College, New York, New York.
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D007167:Immunotherapy; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007893:Leishmania donovani / Q000187:drug effects / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000628:therapy*; D008099:Liver / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C
D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate