Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
Viruses. 2023 Jun 28;15(7):1462. doi: 10.3390/v15071462.
Respiratory pathogens such as influenza and SARS-CoV-2 can cause severe lung infections leading to acute respiratory distress syndrome (ARDS). The pathophysiology of ARDS includes an excessive host immune response, lung epithelial and endothelial cell death and loss of the epithelial and endothelial barrier integrity, culminating in pulmonary oedema and respiratory failure. Traditional approaches for the treatment of respiratory infections include drugs that exert direct anti-pathogen effects (e.g., antivirals). However, such agents are typically ineffective or insufficient after the development of ARDS. Modulation of the host response has emerged as a promising alternative therapeutic approach to mitigate damage to the host for the treatment of respiratory infections; in principle, this strategy should also be less susceptible to the development of pathogen resistance. In this review, we discuss different host-targeting strategies against pathogen-induced ARDS. Developing therapeutics that enhance the host response is a pathogen-agnostic approach that will help prepare for the next pandemic.
呼吸道病原体，如流感病毒和 SARS-CoV-2，可引起严重肺部感染，导致急性呼吸窘迫综合征（ARDS）。ARDS 的病理生理学包括过度的宿主免疫反应、肺上皮细胞和内皮细胞死亡以及上皮和内皮屏障完整性丧失，最终导致肺水肿和呼吸衰竭。治疗呼吸道感染的传统方法包括具有直接抗病原体作用的药物（例如抗病毒药物）。然而，在 ARDS 发生后，这些药物通常无效或不足。宿主反应的调节已成为一种有前途的治疗选择，可减轻宿主的损伤，从而治疗呼吸道感染；从原则上讲，这种策略也不太容易产生病原体耐药性。在这篇综述中，我们讨论了针对病原体引起的 ARDS 的不同宿主靶向策略。开发增强宿主反应的治疗方法是一种无病原体的方法，有助于为下一次大流行做好准备。
