State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai 200237, China.
Sci China Life Sci. 2012 Sep;55(9):800-6. doi: 10.1007/s11427-012-4368-x. Epub 2012 Sep 27.
This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculosis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, IL-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P<0.01) and 0.58 (P<0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P<0.01) and 1.22 (P<0.01) lg CFU, respectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P<0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).
这项研究调查了白细胞介素 (IL)-2 和粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 与抗结核药物异烟肼 (INH) 和利福平 (RIF) 联合治疗结核分枝杆菌 (TB) 感染小鼠模型的治疗效果。使用对利福平敏感的结核分枝杆菌 H37Rv 株感染小鼠，最初根据存活率、肺部和脾脏细菌计数以及肺部病理状况评估 IL-2 和 GM-CSF 的有效性。然后，在耐多药菌株 OB35 感染小鼠中评估免疫治疗方案的疗效。在 H37Rv 感染模型中，IL-2 和 GM-CSF 单独治疗分别使肺部细菌数量减少 0.82 (P<0.01) 和 0.58 (P<0.05) lg 集落形成单位 (CFU)，脾脏细菌数量减少 1.42 (P<0.01) 和 1.22 (P<0.01) lg CFU，与未治疗组相比。与单独接受抗菌治疗的小鼠相比，接受免疫治疗的小鼠肺部病变较少。在 OB35 感染模型中，与未治疗或单独接受抗菌治疗的小鼠相比，两种细胞因子单独免疫治疗均显著降低肺部和脾脏细菌负荷，肺部病变程度较轻。值得注意的是，接受两种细胞因子免疫治疗的小鼠的存活率为 30%，高于其他治疗组，且肺部和脾脏的 CFU 明显减少（分别为 1.02 和 1.34 lg CFU），与单独抗菌治疗相比差异具有统计学意义（P<0.01）。这项研究表明，IL-2 和 GM-CSF 的联合免疫治疗可能对治疗耐多药结核分枝杆菌（MDR-TB）有用。
