INHALED CYTOKINES FOR MYCOBACTERIAL LUNG DISEASE

虽然非结核分枝杆菌（NTM），如鸟-胞内分枝杆菌复合体（MAC），在环境中普遍存在，但由NTM引起的疾病在免疫活性宿主中很少见。然而，局部肺部疾病确实会发生。最常见的受影响的人是不吸烟的老年妇女。由于MAC对抗结核药物的固有抗性和毒性，在非HIV感染患者中治疗MAC引起的肺部疾病通常是困难的。手术和/或通过细胞因子给药的免疫调节已被提议作为此类患者的潜在预防性治疗。在体外，γ-干扰素（γ-IFN）已被证明可以增强巨噬细胞对MAC的杀伤作用。轶事证据表明，这种细胞因子可能用于治疗人类MAC疾病。对于局限于肺部的MAC疾病，给予γ-IFN的雾化制剂是有吸引力的，因为它似乎激活巨噬细胞而不产生全身副作用。为了进一步了解γ-IFN在治疗肺MAC疾病中的潜在效用，将研究雾化γ-IFN对肺泡巨噬细胞的作用。具体而言，将检查雾化γ-IFN增强肺泡巨噬细胞结合和杀死MAC的能力。从这项研究中获得的信息将有助于确定γ-IFN作为老年人肺MAC的连续治疗的潜力。如果γ-干扰素在这方面似乎是有前途的，未来的调查可以针对测试其在肺MAC患者的治疗效果。

Although nontuberculous mycobacteria (NTM), such as Mycobacterium avium-intracellulare complex (MAC), are ubiquitous in the environment, disease caused by NTM is rare in immunocompetent hosts. Localized pulmonary disease, nevertheless, does occur. Most frequently the individuals affected are elderly, non-smoking women. Treatment of pulmonary disease due to MAC in non-HIV-infected patients is typically difficult due to inherent resistance of MAC to anti-tuberculous medications and toxicity. Surgery and/or immunomodulation via cytokine administration have been proposed as potential adjunctive therapies for such patients. In vitro, gamma (y)-interferon (y-IFN) has been shown to enhance killing of MAC by macrophages. Anecdotal evidence suggests that this cytokine may have use in the treatment of MAC disease in humans. For MAC disease limited to the lungs, administration of an aerosolized preparation of y-IFN is appealing because it appears to activate macrophages without producing systemic side effects. In order to gain further insight into the potential utility of y-IFN in the treatment of pulmonary MAC disease, the effect of aerosolized y-IFN on alveolar macrophages will be studied. Specifically, the ability of aerosolized y-IFN to enhance alveolar macrophage binding and killing of MAC will be examined. The information gained from this study will help to determine the potential of y-IFN as an adjunctive therapy for pulmonary MAC in the elderly. If y-IFN appears to be promising in this regard, future investigations can be directed at testing its therapeutic efficacy in pulmonary MAC patients.