Giosuè S, Casarini M, Ameglio F, Zangrilli P, Palla M, Altieri A M, Bisetti A
Istituto Lazzaro Spallanzani, IRCCS, Clinica Malattie dell'Apparato Respiratorio, Via Portuense 292, 00149 Roma (Italia).
Eur Cytokine Netw. 2000 Mar;11(1):99-104.
Multi-drug-resistant tuberculosis (MDR-TB) has emerged as an obstacle to the control of tuberculosis. Recent data however, suggest that interferon-(IFN)-gamma and IFN-alpha may improve disease evolution in subjects affected with pulmonary tuberculosis caused by multi-resistant (IFN-gamma) and sensitive (IFN-alpha) strains. The mechanisms involved are not known, even though it has been reported that IFN-gamma-secreting CD4+ Th cells may possess antitubercular effects. In addition, IFN-alpha can induce IFN-gamma secretion by CD4+ Th cells, and both types of IFN may stimulate macrophage activities. The aim of this study was to explore the possibility that aerosolized IFN-alpha, administered concomitantly with conventional antitubercular chemotherapy, may improve the course of pulmonary tuberculosis. After six months of directly observed therapy (DOT), seven patients who were non-responders to a second line antitubercular therapy were given an IFN-alpha aerosol (3 MU, three times a week) for two months as adjunctive therapy. All strains were resistant to at least two first-line drugs. After IFN-alpha administration, the patients were followed up for a further six months with the same DOT. Sputum samples were collected monthly during the study period, with the exception of the IFN-alpha administration period, when the observations were performed weekly. High resolution computed tomography (HRCT) chest scans were performed before and after IFN-alpha inhalations. The analysis of the results showed that the mean number of Mycobacterium tuberculosis (Mt) had remained statistically unchanged (p = 0.80) during the first 6 months of DOT. During the following 2 months of IFN-alpha administration, 5 patients became negative (p = 0.02). After the end of treatment a progressive increase in Mt number was observed (p = 0. 02). Sputum cultures remained positive for all patients throughout the study period, although a significant decrease (p = 0.02) in the colony number per culture was observed after adjunctive treatment with IFN-alpha. After stopping administration of IFN-alpha, a significant increase (p = 0.03) in the colony number per culture was noted as well as in Mt numbers. HRCT scans were slightly improved in all patients. These preliminary data suggest that aerosolized IFN-alpha may be a promising adjunctive therapy for patients with MDR-TB. Optimal doses and schedules however, require further studies.
耐多药结核病（MDR-TB）已成为结核病控制的一大障碍。然而，近期数据表明，干扰素（IFN）-γ和IFN-α可能改善由耐多药（IFN-γ）和敏感（IFN-α）菌株引起的肺结核患者的病情发展。尽管有报道称分泌IFN-γ的CD4+ Th细胞可能具有抗结核作用，但其中涉及的机制尚不清楚。此外，IFN-α可诱导CD4+ Th细胞分泌IFN-γ，且这两种类型的干扰素均可刺激巨噬细胞活性。本研究的目的是探讨雾化IFN-α与传统抗结核化疗同时使用是否可能改善肺结核病程。在进行了6个月的直接观察治疗（DOT）后，7例对二线抗结核治疗无反应的患者接受了为期2个月的IFN-α雾化治疗（3 MU，每周3次）作为辅助治疗。所有菌株均对至少两种一线药物耐药。给予IFN-α治疗后，对患者继续进行6个月相同的DOT随访。在研究期间，除IFN-α给药期（此期间每周进行观察）外，每月采集痰标本。在IFN-α吸入前后进行胸部高分辨率计算机断层扫描（HRCT）。结果分析显示，在DOT的前6个月，结核分枝杆菌（Mt）的平均数量在统计学上保持不变（p = 0.80）。在随后的2个月IFN-α给药期间，5例患者转阴（p = 0.02）。治疗结束后，观察到Mt数量逐渐增加（p = 0.02）。在整个研究期间，所有患者的痰培养均为阳性，尽管在用IFN-α辅助治疗后，每份培养物中的菌落数显著减少（p = 0.02）。停止给予IFN-α后，每份培养物中的菌落数以及Mt数量均显著增加（p = 0.03）。所有患者的HRCT扫描均略有改善。这些初步数据表明，雾化IFN-α可能是耐多药结核病患者一种有前景的辅助治疗方法。然而，最佳剂量和疗程需要进一步研究。
