Carter K C, Hutchison S, Boitelle A, Murray H W, Sundar S, Mullen A B
Department of Immunology, University of Strathclyde, Glasgow, UK.
Parasitology. 2005 Dec;131(Pt 6):747-57. doi: 10.1017/S0031182005008486.
Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.
用丁硫氨酸亚砜胺的非离子表面活性剂囊泡制剂（BSO-NIV）和葡萄糖酸锑钠（SSG）联合治疗感染不同株杜氏利什曼原虫的小鼠，并未改变Th1或Th2反应指标，但与对照组相比，经处理小鼠的脾细胞受刺激后，IL6水平和亚硝酸盐水平出现了显著的、不依赖菌株的上调。BSO-NIV/SSG治疗的疗效取决于宿主能够产生呼吸爆发，这表明巨噬细胞在控制治疗结果中起重要作用。体外研究表明，SSG耐药性与对活化巨噬细胞、过氧化氢或酒石酸锑钾杀伤的更大抗性有关。纵向研究表明，SSG耐药（SSG-R）株比SSG敏感（SSG-S）株毒性更强，感染后4个月时导致的寄生虫负荷显著更高。这些结果表明，接触SSG可能有利于毒性更强的菌株出现。
