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IL-2和GM-CSF免疫治疗耐多药结核病的研究

, PP. 801-808

Keywords: 结核病,耐多药结核,IL-2,GM-CSF,免疫治疗

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Abstract:

本研究在结核病小鼠模型中评估了白细胞介素-2(IL-2)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)与抗菌药物异烟肼(INH)、利福平(RIF)联合使用治疗结核菌感染的治疗效果.首先,在药物敏感型结核杆菌H37Rv感染小鼠模型中,通过测定存活率、小鼠肺部和脾脏菌落数以及分析肺部组织病理情况评估IL-2和GM-CSF的治疗效果.然后,在耐多药结核菌株OB35感染小鼠模型中评估免疫治疗方案的治疗效果.在H37Rv感染模型中,与非治疗组小鼠相比,经IL-2或GM-CSF单细胞因子治疗后的小鼠肺部的菌落数分别减少了0.82lgCFU(P<0.01)和0.58lgCFU(P<0.05),而脾脏的菌落数分别减少了1.42lgCFU(P<0.01)和1.22lgCFU(P<0.01).虽然当单细胞因子与INH+RIF(HR)联合使用时,并未在抑菌率上表现出任何优势,但是肺部组织病理切片显示联合免疫治疗组小鼠肺部损伤明显减弱.在耐药结核杆菌OB35感染小鼠模型中,和未治疗组以及抗菌药物治疗组相比,免疫治疗能有效降低肺脾菌落数,同时减少肺部损伤.值得一提的是,相对于其他治疗组,两种细胞因子共同参与的免疫治疗能进一步提高小鼠存活率到30%;而且能比单一抗菌药物治疗更有效地减少肺脾菌落数(其中肺部减少1.02lgCFU,脾脏减少1.34lgCFU,P<0.01).该研究表明,IL-2和GM-CSF共同参与的免疫治疗可能是治疗耐药结核病(MDR-TB)的有效策略之一.

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