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研究顺铂+78kDa+MPL-A 免疫化学疗法对 BALB/c 小鼠感染杜氏利什曼原虫的治疗潜力。

To investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kDa + MPL-A against Leishmania donovani in BALB/c mice.

机构信息

Department of Zoology, Panjab University, Chandigarh, India.

出版信息

Parasite Immunol. 2014 Jan;36(1):3-12. doi: 10.1111/pim.12071.

Abstract

Leishmaniasis has recently garnered attention as one of the diseases 'most neglected' by drug research and development, as the current therapeutic modalities available for the patients are ridden with unacceptable toxicity due to high dosage of the drug, prolonged treatment schedules, resistance and prohibitive costs. A successful chemotherapy requires a restoration of immune response; therefore, we combined Leishmania-specific 78 kDa antigen (with or without adjuvant MPL-A) along with a novel drug cisplatin in infected BALB/c mice and did its comparative analysis with chemotherapy and immunotherapy alone. Animals that were treated with immunochemotherapy showed maximum curative potential as demonstrated by a marked reduction in parasite load. Delayed-type hypersensitivity response to leishmanial antigens has been widely used to assess the level of host protection to the disease. An increased delayed-type hypersensitivity (DTH) response was observed in animals given immunotherapy or chemotherapy or immunochemotherapy; however, maximum DTH response was observed in animals treated with cisplatin + 78 kDa + MPL-A. These animals were also found to exhibit higher IgG2a levels greater cytokine (IFN-γ and IL-2) concentrations suggesting the generation of a strong Th1 type of immune response which is responsible for resolution of the disease.

摘要

利什曼病最近作为药物研发中“最被忽视”的疾病之一引起了关注,因为目前可供患者使用的治疗方法因药物剂量高、治疗方案延长、耐药性和高昂的成本而存在不可接受的毒性。成功的化疗需要恢复免疫反应;因此,我们将利什曼原虫特异性 78 kDa 抗原(有或没有佐剂 MPL-A)与新型药物顺铂联合用于感染 BALB/c 小鼠,并与单独化疗和免疫治疗进行了比较分析。接受免疫化学疗法治疗的动物表现出最大的治愈潜力,寄生虫负荷明显减少。迟发型超敏反应对利什曼原虫抗原的反应已广泛用于评估宿主对疾病的保护水平。在接受免疫治疗、化疗或免疫化学治疗的动物中观察到迟发型超敏(DTH)反应增加;然而,在接受顺铂+78 kDa+MPL-A 治疗的动物中观察到最大的 DTH 反应。还发现这些动物表现出更高的 IgG2a 水平和更高的细胞因子(IFN-γ 和 IL-2)浓度,表明产生了强烈的 Th1 型免疫反应,这是疾病消退的原因。

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