Immunochemotherapy for intracellular Leishmania donovani infection: gamma interferon plus pentavalent antimony.
To determine if the macrophage-activating T cell lymphokine gamma interferon (IFN-gamma) can enhance the effect of conventional chemotherapy against intracellular Leishmania donovani, we treated human macrophages in vitro with both recombinant (r) IFN-gamma and sodium stibogluconate (Pentostam). After pretreatment with a nonactivating dose of rIFN-gamma (10 U/mL), ineffective concentrations of Pentostam (1 and 5 micrograms/mL) were converted to leishmanistatic concentrations, and a leishmanistatic dose (10 micrograms/mL) was converted to uptake of Pentostam. In a model of visceral leishmaniasis, infected mice were treated with ineffective concentrations of rIFN-gamma (10(4) U) plus suboptimal doses of Pentostam (10 or 50 mg/kg). With combination therapy, the doses of Pentostam required to achieve 50% inhibition or killing of visceral L. donovani were reduced by 10-fold and fourfold, respectively. These results suggest that IFN-gamma therapy may be a useful adjunct in visceral leishmaniasis and illustrate one potential role for IFN-gamma in the treatment of systemic intracellular infections.
Murray
H W
HW
Division of Infectious Diseases, Cornell University, Medical College, New York, New York 10021.
Berman
J D
JD
Wright
S D
SD
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005942:Gluconates / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000628:therapy*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
D005942:Gluconates; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate