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次优剂量的葡萄糖酸锑钠(SAG)-双过氧钒酸盐组合通过扩大抗利什曼原虫T细胞库并提高IFN-γ与IL-10的比例,清除感染了抗锑杜氏利什曼原虫的BALB/c小鼠体内的器官寄生虫。

Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-gamma to IL-10 ratio.

作者信息

Haldar Arun Kumar, Banerjee Subha, Naskar Kshudiram, Kalita Diganta, Islam Nashreen S, Roy Syamal

机构信息

Department of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, West Bengal 700 032, India.

出版信息

Exp Parasitol. 2009 Jun;122(2):145-54. doi: 10.1016/j.exppara.2009.02.001.

Abstract

We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb(R)) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.

摘要

我们证明,次优剂量的葡萄糖酸锑钠(SAG)与过氧钒酸盐化合物K[VO(O2)2(H2O)](也称为PV6)联合使用,在对抗BALB/c小鼠的抗锑性杜氏利什曼原虫(LD)实验感染方面非常有效,这从器官寄生虫负荷的显著降低中可以明显看出,而SAG基本上无效。有趣的是,这种治疗还允许抗利什曼原虫T细胞克隆扩增,同时伴随着IFN-γ的强劲激增和IL-10产生的相应减少。与感染组相比,经治疗动物的脾细胞产生的IFN-γ诱导的杀寄生虫效应分子(如超氧化物和一氧化氮)的量显著更高。我们的研究表明,次优剂量的SAG和PV6联合使用可能有利于治疗对SAG耐药的内脏利什曼病患者。

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