Study for therapy in COPD patients by regulating proinflammatory cytokine and oxidant stress

COPD是一种多种症状并存的疾病，众所周知，这些症状会影响任何一个COPD患者的预后。常见的共存症状包括动脉硬化、高血压、肺心病和右心衰竭、其他心血管系统损害、高脂血症、糖尿病、骨质疏松症、消瘦和抑郁。因此，COPD的治疗需要考虑肺部症状以及其他共存条件。我们之前曾报道过，戒烟并不能改善重症COPD患者的肺部炎症。在我们的研究中，我们发现细胞因子白介素18(IL-18)在COPD患者肺组织的肺泡巨噬细胞、CD8~+T细胞以及细支气管壁和肺泡上皮细胞中都有较强的表达。在小鼠中，肺内结构性IL-18过度产生导致肺部炎症，出现CD8~+T细胞、巨噬细胞、中性粒细胞和嗜酸性粒细胞。老年IL-18Tg小鼠出现肺体积增大、严重的肺气肿改变、右心室扩张和轻度的肺动脉高压。基于这些发现，我们推测IL-18可能参与了COPD共存症状的发生和发展。我们先前在小鼠模型中确定硫氧还蛋白1(TRX1)可抑制弹性酶诱导的肺部炎症和肺气肿改变。我们将利用弹性酶诱导的肺气肿模型来确定TRX1是否代表一种可能的治疗COPD共存症状的新方法。

COPD is a disorder with several coexisting symptoms, and these symptoms are known to influence the prognosis of any individual COPD patient. Common coexisting symptoms include arterial sclerosis, hypertension, cor pulmonale and right heart failure, other cardiovascular system lesions, hyperlipemia, diabetes mellitus, osteoporosis, emaciation, and depression. Therefore, treatment of COPD needs to consider pulmonary symptoms in addition to other co-existing conditions.We previously reported that pulmonary inflammation in patients with severe COPD was not improved by the cessation of smoking. In our studies, we found that the cytokine Interleukin-18 (IL-18) was strongly expressed in alveolar macrophages, CD8^+ T cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. In mice, constitutive IL-18 overproduction in the lungs resulted in pulmonary inflammation with the appearance of CD8^+ T cells, macrophages, neutrophils, and eosinophils. Enlarged lung volume, severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension were observed in aged IL-18 Tg mice. Based on these finding, we hypothesize that IL-18 may contribute to the onset / development of the coexistence symptoms of COPD. We previously determined that thioredoxin1 (TRX1) inhibits elastase-induced pulmonary inflammation and emphysematous changes in a mouse model. We will utilize the elastase-induced emphysema model in order to determine if TRX1 represents a possible new treatment of the coexisting symptoms in COPD.