Enhancement of Glucantime® Therapy of Murine Leishmania Donovani Infection by a Synthetic Immunopotentiating Compound (CP-46,665-1)

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  • Department of Microbiology and Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524

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.

Author Notes

Permanent address: Clinica Malattie Tropicali e Subtropicali, Ia Facolta' di Medicina e Chirurgia, Universita' di Napoli, Via Cotugno, 1, 80135 Napoli, Italia.

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