Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, Edinburgh, UK.
Int J Chron Obstruct Pulmon Dis. 2010 Sep 7;5:297-309. doi: 10.2147/copd.s7390.
Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal and chronic inflammatory response in the lung that underlies the chronic airflow obstruction of the small airways, the inexorable decline of lung function, and the severity of the disease. The control of this inflammation remains a key strategy for treating the disease; however, there are no current anti-inflammatory treatments that are effective. Although glucocorticoids (GCs) effectively control inflammation in many diseases such as asthma, they are less effective in COPD. The molecular mechanisms that contribute to the development of this relative GC-insensitive inflammation in the lung of patients with COPD remain unclear. However, recent studies have indicated novel mechanisms and possible therapeutic strategies. One of the major mechanisms proposed is an oxidant-mediated alteration in the signaling pathways in the inflammatory cells in the lung, which may result in the impairment of repressor proteins used by the GC receptor to inhibit the transcription of proinflammatory genes. Although these studies have described mechanisms and targets by which GC function can be restored in cells from patients with COPD, more work is needed to completely elucidate these and other pathways that may be involved in order to allow for more confident therapeutic targeting. Given the relative GC-insensitive nature of the inflammation in COPD, a combination of therapies in addition to a restoration of GC function, including effective alternative anti-inflammatory targets, antioxidants, and proresolving therapeutic strategies, is likely to provide better targeting and improvement in the management of the disease.
慢性阻塞性肺疾病（COPD）的特征是肺部异常和慢性炎症反应，这是小气道慢性气流阻塞、肺功能不可避免下降和疾病严重程度的基础。控制这种炎症仍然是治疗疾病的关键策略；然而，目前没有有效的抗炎治疗方法。尽管糖皮质激素（GCs）在哮喘等许多疾病中能有效控制炎症，但在 COPD 中效果较差。导致 COPD 患者肺部这种相对 GC 不敏感炎症发展的分子机制仍不清楚。然而，最近的研究表明了新的机制和可能的治疗策略。提出的主要机制之一是肺部炎症细胞中信号通路的氧化介导改变，这可能导致 GC 受体用于抑制促炎基因转录的抑制蛋白受损。尽管这些研究已经描述了可以恢复 COPD 患者细胞中 GC 功能的机制和靶点，但仍需要更多的工作来完全阐明这些和其他可能涉及的途径，以便更有信心地进行治疗靶向。鉴于 COPD 中炎症的相对 GC 不敏感性，除了恢复 GC 功能之外，联合治疗，包括有效的替代抗炎靶点、抗氧化剂和促解决治疗策略，可能会提供更好的靶向治疗和改善疾病的管理。
