S. Buates et G. Matlashewski, Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: Efficacy and mode of action, J INFEC DIS, 179(6), 1999, pp. 1485-1494
There is a need for new, effective, and less toxic treatments for leishmani
asis, an infectious disease caused by Leishmania protozoa and is a major ca
use of suffering and morbidity in much of the developing world. Imiquimod,
an immune-response modifier, has recently been approved by the Food and Dru
g Administration for the treatment of genital warts caused by human papillo
maviruses. Imiquimod initiates a local immune reaction, including the stimu
lation of macrophages, resulting in resolution of human papillomavirus infe
ction and regression of the viral lesion. Since imiquimod activates a numbe
r of immune cells, including macrophages, which are the only host cells of
Leishmania species, an investigation was done to determine whether it induc
es leishmanicidal properties in infected macrophages in vitro and in vivo i
n a mouse model. Imiquimod and a related compound, S-28463, effectively sti
mulated leishmanicidal activity in macrophages; moreover, imiquimod stimula
ted signal transduction associated with inducing nitric oxide synthesis in
macrophages.