Synergism of IL-2-stimulated splenocytes and Pentostam enhances the killing of Leishmania donovani in vitro.
Control of infections by the obligate intramacrophage protozoan parasite Leishmania donovani is traditionally done with pentavalent antimonial drugs. It was of interest to determine if immunotherapy with IL-2-stimulated splenocytes would enhance drug action in an in vitro model system. It is confirmed that nontoxic doses of Pentostam decrease infection in a dose-dependent manner in vitro in terms of both the number of amastigotes/100 macrophages and the % of infected macrophages; the curative effect was most apparent when the drug was used on the 7th day of the infection, when the parasite was in its proliferative phase. It is also confirmed that recombinant IL-2-stimulated splenocytes induced infected macrophages to reduce significantly their parasite burden, especially when the infection was treated in the nonproliferative phase of the parasite, also in a dose-dependent manner. Leishmanicidal action in the infected macrophages was induced by cytokine(s) released from the lymphokine-stimulated cells. Immunotherapy in the nonproliferative phase, combined with drug treatment in the proliferative phase, reduced the infection to levels significantly below those produced by either treatment alone. Immunotherapy with IL-2-stimulated splenocytes in combination with Pentostam is, therefore, an excellent candidate treatment for the effective reduction of experimental infections by L. donovani.
Eslami
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Institute of Parasitology of McGill University, Macdonald Campus, Québec, Canada.
Gaucher
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Tanner
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D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage*; D007893:Leishmania donovani / Q000187:drug effects* / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology*; D013997:Time Factors
D000981:Antiprotozoal Agents; D007376:Interleukin-2; D000967:Antimony Sodium Gluconate