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      Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: efficacy and mode of action.

      The Journal of Infectious Diseases

      therapeutic use, Trypanocidal Agents, Signal Transduction, biosynthesis, Proto-Oncogene Proteins c-fos, Mice, Inbred BALB C, Mice, parasitology, immunology, Macrophages, drug therapy, Leishmaniasis, drug effects, Leishmania donovani, Female, Bone Marrow Cells, Animals, Aminoquinolines, Adjuvants, Immunologic

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          Abstract

          There is a need for new, effective, and less toxic treatments for leishmaniasis, an infectious disease caused by Leishmania protozoa and is a major cause of suffering and morbidity in much of the developing world. Imiquimod, an immune-response modifier, has recently been approved by the Food and Drug Administration for the treatment of genital warts caused by human papillomaviruses. Imiquimod initiates a local immune reaction, including the stimulation of macrophages, resulting in resolution of human papillomavirus infection and regression of the viral lesion. Since imiquimod activates a number of immune cells, including macrophages, which are the only host cells of Leishmania species, an investigation was done to determine whether it induces leishmanicidal properties in infected macrophages in vitro and in vivo in a mouse model. Imiquimod and a related compound, S-28463, effectively stimulated leishmanicidal activity in macrophages; moreover, imiquimod stimulated signal transduction associated with inducing nitric oxide synthesis in macrophages.

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          Journal
          10.1086/314782
          10228071

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