Sachdeva Heena, Sehgal Rakesh, Kaur Sukhbir
Department of Zoology, Panjab University, Chandigarh 160014, India.
Parasitol Int. 2014 Feb;63(1):21-30. doi: 10.1016/j.parint.2013.09.016. Epub 2013 Oct 6.
Current drugs for the treatment of visceral leishmaniasis are inadequate and their efficacies are also compromised due to suppression of immune function associated during the course of infection. To overcome this problem, efforts are needed to develop therapies with effective immunomodulatory agents where decrease of parasitic burden and simultaneous enhancement of adaptive immunity can be achieved. In this study we have evaluated a new therapeutic approach based on combination of Asparagus racemosus, an immunomodulatory drug, in combination with cisplatin against Leishmania donovani infected BALB/c mice. We demonstrate that A. racemosus (650 mg/kg b.wt./day for 15 days, orally) in combination with cisplatin (5 mg/kg b.wt./day for 5 days, intraperitoneally) enhanced the clearance of parasites as determined by Giemsa-stained liver impression smears. Besides having better killing activity, this combination group achieved increased production of disease resolving Th-1 response (IFN-gamma, IL-2), heightened DTH (delayed type hypersensitivity) response and augmented levels of IgG2a. Moreover, A. racemosus in combination with cisplatin not only provided enhanced protective immune response but also resulted in remarkable improved kidney and liver function tests as manifested by normal levels of SGOT, SGPT, alkaline phosphatase, creatinine and urea in blood plasma with normal histological observations as compared to only cisplatin treated L. donovani infected BALB/c mice. Through this study we have ascertained that A. racemosus in combination with cisplatin in L. donovani infected BALB/c mice boosted as well as restored both cellular and humoral immunity. Thus in view of severe immunosuppression in visceral leishmaniasis, a better and effective strategy for optimum efficacy of future antileishmanial drugs would direct not only killing of parasite by the drug, but also simultaneous generation of immunity against the disease.
目前用于治疗内脏利什曼病的药物并不理想，而且由于感染过程中免疫功能受到抑制，其疗效也大打折扣。为克服这一问题，需要努力研发含有有效免疫调节剂的疗法，以实现降低寄生虫负荷并同时增强适应性免疫的目标。在本研究中，我们评估了一种基于免疫调节药物石刁柏与顺铂联合使用的新治疗方法，用于治疗感染杜氏利什曼原虫的BALB/c小鼠。我们证明，石刁柏（650毫克/千克体重/天，口服，共15天）与顺铂（5毫克/千克体重/天，腹腔注射，共5天）联合使用，通过吉姆萨染色的肝脏印片涂片检测发现，可增强寄生虫的清除效果。除了具有更好的杀虫活性外，该联合用药组还使疾病消退性Th-1反应（IFN-γ、IL-2）的产生增加、迟发型超敏反应（DTH）增强以及IgG2a水平升高。此外, 与仅用顺铂治疗的感染杜氏利什曼原虫的BALB/c小鼠相比，石刁柏与顺铂联合使用不仅提供了增强的保护性免疫反应，还使肾脏和肝脏功能测试结果显著改善,血浆中的谷草转氨酶、谷丙转氨酶、碱性磷酸酶、肌酐和尿素水平正常,组织学观察也正常。通过本研究我们确定，在感染杜氏利什曼原虫的BALB/c小鼠中，石刁柏与顺铂联合使用可增强并恢复细胞免疫和体液免疫。因此，鉴于内脏利什曼病存在严重的免疫抑制情况，未来抗利什曼病药物要达到最佳疗效，更好且有效的策略不仅是药物杀死寄生虫，还要同时产生针对该疾病的免疫力。
