Activity of the novel immunomodulatory compound tucaresol against experimental visceral leishmaniasis.
Tucaresol, a novel immunomodulator, was inactive against Leishmania donovani amastigotes in both peritoneal and bone marrow macrophages in vitro at concentrations between 100 and 1 microM, with toxicity to macrophages and parasites at 300 microM. However, against L. donovani in BALB/c mice at doses between 80 and 1.25 mg/kg of body weight administered once daily by the oral route during days 7 to 11 of infection, an optimal dose of 5 mg/kg produced a 43.8 to 62.4% suppression of liver amastigotes, with significantly reduced activity at the extremes of the dose range. This response was not related to levels of infection. No interaction with the standard pentavalent antimonial sodium stibogluconate (Pentostam) was observed during this period of infection. The optimum dose of 5 mg/kg was ineffective when administered during the first week of infection and was most effective against the liver infection when administered during weeks 2 to 3 of infection (42.3 to 46.8% inhibition) and against the splenic infection when administered during week 6 of infection (59.5% inhibition). The optimum dose of tucaresol against L. donovani in C57BL/6 mice was 5 mg/kg, which produced a 40.8 to 48.7% suppression of liver amastigotes when administered in a range of 80 to 1.25 mg/kg during days 7 to 11 of infection. The drug had no activity against L. donovani infections in C.B-17 scid mice when the same regimen was used.
Smith
A C
AC
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
Yardley
V
V
Rhodes
J
J
Croft
S L
SL
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D001547:Benzaldehydes; D001565:Benzoates; C059629:tucaresol