Hou Jiang-hou, Li Qi, Lu Yu, Zheng Mei-qin, Zhao Wei-jie, Xu Jian
Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2012 Dec;35(12):911-4.
To investigate the effect of adjunctive therapy by immune agents in mice infected with multidrug-resistant tuberculosis (MDR-TB).
Sixty-eight adult male BALB/c mice were infected with multidrug-resistant Mycobacterium tuberculosis (MTB) by aerosol route. The mice were randomly divided into a control group, an immuno-treatment group, a drug treatment group and a combination treatment group (drug plus immuno-treatment). In each treatment group, 16 mice were treated at day 21 after infection, and another 4 mice were sacrificed at day 21 after infection (treatment for 0 week) as the blank control group. In the treatment group, 4 mice were sacrificed in turn at the day after treatment for 4, 8, 16 and 20 weeks. Lung and spleen mass index at the day after treatment for 8, 16 and 20 weeks, lung and spleen live bacterial count in each period, serum IFN-γ and IL-10 levels at the day after treatment for 8 weeks were measured. Comparisons of analyzed parameters among groups were performed with the one way ANOVA test, and comparisons of parameters between 2 groups were performed with SNK and Games-Howell test.
The lung mass index in the immuno-treatment group (0.66 ± 0.09)%, drug group (0.60 ± 0.07)% and combination therapy group (0.57 ± 0.05)% at the day after treatment for 8 weeks were significantly lower than that of the control group (0.81 ± 0.09)%, (F = 7.364, P < 0.01). Spleen CFU of immuno-treatment group at 16 and 20 weeks [(3.11 ± 0.14) lg CFU and (3.15 ± 0.18) lg CFU] were significantly lower than those of the control group [(3.77 ± 0.35) lg CFU and (4.31 ± 0.06)] (F values were 446.424 and 2107.689, P < 0.01). Spleen tissues of the drug group and the combination therapy group were sterile from 4 weeks. The serum IFN-γ levels of immuno-treatment group, drug group and combination therapy were (5.3 ± 1.9) ng/L, (1.3 ± 0.5) ng/L and (0.9 ± 1.3) ng/L, respectively, being significantly lower than that of the control group (10.3 ± 2.1) ng/L (F = 32.128, P < 0.01). The lung and spleen mass index, lung and spleen CFU, serum IFN-γ and IL-10 between medication group and combination therapy showed no significant differences.
Immuno-treatment could mitigate lung tissue inflammation, reduce the number of MTB in mouse spleen tissues and decrease serum IFN-γ levels in the MDR-TB mouse model. However immuno-treatment failed to reduce the number of MTB in lung tissues. There was no adjunctive effect of immuno treatment for MDR-TB mice in reducing the number of MTB and mitigating inflammation.
探讨免疫制剂辅助治疗对耐多药结核病（MDR-TB）感染小鼠的影响。
68只成年雄性BALB/c小鼠经气溶胶途径感染耐多药结核分枝杆菌（MTB）。将小鼠随机分为对照组、免疫治疗组、药物治疗组和联合治疗组（药物加免疫治疗）。各治疗组在感染后第21天开始治疗，另4只小鼠在感染后第21天（治疗0周）处死作为空白对照组。治疗组在治疗4、8、16和20周后的次日依次处死4只小鼠。测量治疗8、16和20周后次日的肺和脾质量指数、各时期肺和脾活菌数、治疗8周后次日的血清IFN-γ和IL-10水平。组间分析参数比较采用单因素方差分析，两组参数比较采用SNK和Games-Howell检验。
治疗8周后次日，免疫治疗组（0.66±0.09）%、药物组（0.60±0.07）%和联合治疗组（0.57±0.05）%的肺质量指数显著低于对照组（0.81±0.09）%，（F=7.364，P<0.01）。免疫治疗组16周和20周时的脾脏CFU[（3.11±0.14）lg CFU和（3.15±0.18）lg CFU]显著低于对照组[（3.77±0.35）lg CFU和（4.31±0.06）]（F值分别为446.424和2107.689，P<0.01）。药物组和联合治疗组的脾脏组织从4周起无菌。免疫治疗组、药物组和联合治疗组的血清IFN-γ水平分别为（5.3±1.9）ng/L、（1.3±0.5）ng/L和（0.9±1.3）ng/L，显著低于对照组（10.3±2.1）ng/L（F=32.128，P<0.01）。用药组和联合治疗组之间的肺和脾质量指数、肺和脾CFU、血清IFN-γ和IL-10无显著差异。
在耐多药结核病小鼠模型中，免疫治疗可减轻肺组织炎症，减少小鼠脾脏组织中MTB的数量，降低血清IFN-γ水平。然而，免疫治疗未能减少肺组织中MTB的数量。免疫治疗对耐多药结核病小鼠在减少MTB数量和减轻炎症方面无辅助作用。
