Buates S, Matlashewski G
Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9.
J Infect Dis. 1999 Jun;179(6):1485-94. doi: 10.1086/314782.
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.
利什曼病是一种由利什曼原虫引起的传染病，在许多发展中国家是痛苦和发病的主要原因，因此需要新的、有效的且毒性较小的治疗方法。咪喹莫特是一种免疫反应调节剂，最近已被美国食品药品监督管理局批准用于治疗由人乳头瘤病毒引起的尖锐湿疣。咪喹莫特引发局部免疫反应，包括刺激巨噬细胞，从而导致人乳头瘤病毒感染的消退和病毒病变的消退。由于咪喹莫特可激活包括巨噬细胞在内的多种免疫细胞，而巨噬细胞是利什曼原虫的唯一宿主细胞，因此开展了一项研究以确定它是否在体外感染的巨噬细胞以及小鼠模型的体内诱导杀利什曼原虫特性。咪喹莫特和一种相关化合物S-28463可有效刺激巨噬细胞中的杀利什曼原虫活性；此外，咪喹莫特刺激与诱导巨噬细胞中一氧化氮合成相关的信号转导。
