Enhancement of Glucantime therapy of murine Leishmania donovani infection by a synthetic immunopotentiating compound (CP-46,665-1).
The therapeutic efficacy of CP-46,665-1, a synthetic lipoidal amine with proven immunomodulatory and anti-tumor properties, in combination with chemotherapy was evaluated in L. donovani-infected C57Bl/6 mice. Immunostimulation and drug treatment resulted in a 10-fold lesser infection level than in untreated mice, while animals treated with Glucantime alone exhibited only a modest amelioration of the infection. We also studied the capacity of CP-elicited peritoneal macrophages of C57Bl/6 mice cultured alone or in combination with Glucantime and/or lymphokine to eliminate intracellular L. donovani amastigotes. When CP-elicited cells were incubated with Glucantime, they exhibited a significantly higher killing potential than did drug treated thioglycollate-elicited cells. CP-macrophages stimulated with lymphokine alone or in combination with antimonial drug, killed amastigotes more rapidly and efficiently than similarly treated thioglycollate-elicited macrophages. In vivo and in vitro results of this study show that a combined regimen of immunostimulation with CP and antimonial drug is more effective in treatment of L. donovani infection than either treatment alone.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000965:Antimony / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D007891:Leishmania / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008222:Lymphokines / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000469:parasitology; D008536:Meglumine; D000077485:Meglumine Antimoniate; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds; D010880:Piperidines / Q000627:therapeutic use*; D013864:Thioglycolates / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000981:Antiprotozoal Agents; D008222:Lymphokines; D009942:Organometallic Compounds; D010880:Piperidines; D013864:Thioglycolates; D008536:Meglumine; C038408:CP 46665; D000077485:Meglumine Antimoniate; D000965:Antimony