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）...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 tuberculo- sis （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, 1L-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, re- spectively, 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）.展开更多
目的评价外周血及脑脊液结核感染T淋巴细胞斑点试验(T cells spot test of tuberculosis infection,T-SPOT.TB)对结核性脑膜炎的诊断价值。方法2013年3月至2017年3月复旦大学附属华山医院临床疑似结核性脑膜炎患者115例,最终确诊为结核...目的评价外周血及脑脊液结核感染T淋巴细胞斑点试验(T cells spot test of tuberculosis infection,T-SPOT.TB)对结核性脑膜炎的诊断价值。方法2013年3月至2017年3月复旦大学附属华山医院临床疑似结核性脑膜炎患者115例,最终确诊为结核性脑膜炎患者30例,非结核性感染性脑膜炎患者37例,非感染性脑膜炎患者29例。采用Fisher确切概率法评价外周血及脑脊液T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值,采用受试者工作特征(receiver operating characteristic curve,ROC)曲线下面积(area under the curve,AUC)评估外周血及脑脊液T-SPOT.TB的诊断效能。结果30例结核性脑膜炎和66例非结核性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、77.0%、65.9%和95.9%,脑脊液T-SPOT.TB分别为66.7%、87.7%、71.4%和85.1%。30例结核性脑膜炎和37例其他感染性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、68.6%、71.1%和92.3%,脑脊液T-SPOT.TB分别为66.7%、86.5%、80.0%和76.2%。外周血及脑脊液T-SPOT.TB的AUC分别为0.882(95%CI:0.795~0.969)和0.814(95%CI:0.704~0.925)。脑脊液T-SPOT.TB诊断结核性脑膜炎的临界值为8SFC/2.5×105个细胞时,脑脊液T-SPOT.TB的敏感度为66.7%,特异度为91.9%,阳性预测值为87.0%,阴性预测值为77.3%,阳性似然比达8.22,阴性似然比为0.363。结论脑脊液T-SPOT.TB对结核性脑膜炎有一定的诊断价值,且8SFC/2.5×105个细胞可能是区分结核和非结核性脑膜炎的参考临界值。展开更多
基金supported in part by the Key Technologies Research and Development Program for Infectious Diseases of China (Grant No. 2012ZX10003001)the Key Project of Science and Technology of Shanghai (Grant No.10411955000)the Shanghai Science and Technology Development Funds (Grant No. 10XD1400900)
文摘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 tuberculo- sis （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, 1L-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, re- spectively, 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）.
文摘目的评价外周血及脑脊液结核感染T淋巴细胞斑点试验(T cells spot test of tuberculosis infection,T-SPOT.TB)对结核性脑膜炎的诊断价值。方法2013年3月至2017年3月复旦大学附属华山医院临床疑似结核性脑膜炎患者115例,最终确诊为结核性脑膜炎患者30例,非结核性感染性脑膜炎患者37例,非感染性脑膜炎患者29例。采用Fisher确切概率法评价外周血及脑脊液T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值,采用受试者工作特征(receiver operating characteristic curve,ROC)曲线下面积(area under the curve,AUC)评估外周血及脑脊液T-SPOT.TB的诊断效能。结果30例结核性脑膜炎和66例非结核性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、77.0%、65.9%和95.9%,脑脊液T-SPOT.TB分别为66.7%、87.7%、71.4%和85.1%。30例结核性脑膜炎和37例其他感染性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、68.6%、71.1%和92.3%,脑脊液T-SPOT.TB分别为66.7%、86.5%、80.0%和76.2%。外周血及脑脊液T-SPOT.TB的AUC分别为0.882(95%CI:0.795~0.969)和0.814(95%CI:0.704~0.925)。脑脊液T-SPOT.TB诊断结核性脑膜炎的临界值为8SFC/2.5×105个细胞时,脑脊液T-SPOT.TB的敏感度为66.7%,特异度为91.9%,阳性预测值为87.0%,阴性预测值为77.3%,阳性似然比达8.22,阴性似然比为0.363。结论脑脊液T-SPOT.TB对结核性脑膜炎有一定的诊断价值,且8SFC/2.5×105个细胞可能是区分结核和非结核性脑膜炎的参考临界值。
