Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, United States.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, United States.
Arch Bronconeumol (Engl Ed). 2020 Sep;56(9):586-591. doi: 10.1016/j.arbres.2020.04.019. Epub 2020 May 13.
Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as "cytokine storm", occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.
流感病毒感染的特征是症状从轻度充血和身体疼痛到严重肺水肿和呼吸衰竭不等。虽然大多数接触者只有轻微症状，且发病率低，但全球每年估计有 50 万人死于与 IAV 相关的并发症。在这些严重病例中，会发生称为“细胞因子风暴”的过度炎症反应，导致呼吸道上皮屏障受损和急性呼吸窘迫综合征 (ARDS) 的发展。来自回顾性人类研究和流感病毒感染的实验动物模型的数据强调了过度和不足的免疫反应之间的细微差别，宿主反应必须在清除病毒与过度炎症之间取得平衡。目前用于炎症的药理学调节剂，包括皮质类固醇和他汀类药物，在改善流感病毒感染期间的结果方面并不成功。我们已经报告说，炎症反应的幅度受线性泛素组装复合物 (LUBAC) 活性的调节，并且在严重流感病毒感染期间抑制 LUBAC 活性具有保护作用。调节 LUBAC 活性的治疗可能对改善严重流感病毒感染期间的结果至关重要，因为它是宿主反应的分子变阻器。在这里，我们回顾了调节炎症以改善流感病毒感染引起的肺损伤的证据，讨论了当前抗炎策略的数据，并探讨了靶向病毒炎症和改善结果的新途径。
