Condos R, Rom W N, Schluger N W
Bellevue Chest Service, New York, NY, USA.
Lancet. 1997 May 24;349(9064):1513-5. doi: 10.1016/S0140-6736(96)12273-X.
Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-gamma, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis. We investigated safety and tolerability of aerosolised interferon-gamma in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades.
We did an open-label trial of aerosol interferon-gamma given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-gamma 500 micrograms three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended.
Interferon-gamma was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended.
Preliminary data suggest that aerosol interferon-gamma is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.
尽管进行了药物治疗，但耐多药结核病（MDR-TB）仍会导致严重发病。干扰素-γ主要由CD4 T淋巴细胞产生，可激活肺泡巨噬细胞，而肺泡巨噬细胞是宿主抗结核分枝杆菌免疫中的重要效应细胞。我们调查了雾化干扰素-γ对耐多药结核病患者的安全性和耐受性，并根据痰涂片分级评估了其疗效。
我们进行了一项开放标签试验，给予5例痰涂片和培养均为肺部耐多药结核病阳性的患者雾化干扰素-γ，尽管他们有记录显示坚持治疗。患者每周接受3次500微克的雾化干扰素-γ，共1个月。评估安全性和耐受性，除常规临床评估外，在入组时和每周收集痰标本进行涂片和培养。在基线和治疗结束后进行胸部计算机断层扫描。
所有患者对干扰素-γ耐受性良好。所有5例患者体重均稳定或增加。所有患者的痰抗酸杆菌涂片均转为阴性，培养转为阳性的时间延长（从17天至24天，无显著差异），这表明分枝杆菌负荷有所降低。治疗结束2个月后，所有患者的空洞性病变大小均减小。
初步数据表明，雾化干扰素-γ是一种耐受性良好的治疗方法，对于其他治疗反应不佳的耐多药结核病患者，可能作为辅助治疗有用。
