Activity of Antileishmanial Agents against Amastigotes in Human Monocyte-Derived Macrophages and in Mouse Peritoneal Macrophages

Abstract

Leishmania multiplying within either human monocyte-derived macrophages (HM) or mouse peritoneal exudate cells (PEC) were recently shown to be susceptible to pentavalent antimony (Sb) by several investigators. The Sb susceptibilities of 5 cutaneous strains of Leishmania were compared in the 2 model systems, with infection of the macrophages initiated with either amastigotes or promastigotes. The susceptibility to Sb of amastigote-induced infections was statistically the same as the susceptibility of promastigote-induced infections for 4 strains in the PEC model, and for 3 of 4 strains in the HM model. Promastigote-induced infections with the 5th strain were nonviable in both macrophage types. The susceptibility of Leishmania to Sb within PEC was the same statistically as that of organisms within HM for amastigote-induced infections for 4 of 5 strains and for promastigote-induced infections by 3 of 4 strains. The susceptibilities of organisms to Sb within PEC and HM were generally comparable. Either amastigotes or viable promastigotes could be used to initiate the infection. The several technical advantages of the PEC model may make it more useful than the HM model for testing susceptibility to Sb. The modest susceptibility of some strains in both models to the peak serum amounts of antimony which may be achieved by presently recommended treatment regimes may partially explain the high current failure rate in simple cutaneous disease. The susceptibility of one strain within peritoneal cells to primaquine and WR 6026 (8-aminoquinolines), ketoconazole (an imidazole) and formycin B (an inosine analog) was similar to that previously reported in human macrophages. Organisms within peritoneal cells were relatively resistant to peak achievable serum amounts of pentamidine (a diamidine). The antileishmanial activity of 3 of the latter 4 tested classes of compounds probably can be evaluated in either the PEC or the HM models.