Yonker Lael M, Barrios Juliana, Mou Hongmei, Hurley Bryan P
Massachusetts General Hospital, Department of Pediatrics, Pulmonary Division, Boston, Massachusetts, USA.
Massachusetts General Hospital, Mucosal Immunology and Biology Research Center, Boston, Massachusetts, USA.
Clin Pharmacol Ther. 2021 Jul;110(1):69-81. doi: 10.1002/cpt.2165. Epub 2021 Feb 13.
Inflammation of the airway involves the recruitment of highly active immune cells to combat and clear microbes and toxic factors; however, this inflammatory response can result in unintended damage to lung tissue. Tissue damage resulting from inflammation is often mitigated by resolving factors that limit the scope and duration of the inflammatory response. Both inflammatory and resolving processes require the actions of a vast array of lipid mediators that can be rapidly synthesized through a variety of airway resident and infiltrating immune cells. Eicosanoids and endocannabinoids represent two major classes of lipid mediators that share synthetic enzymes and have diverse and overlapping functions. This review seeks to provide a summary of the major bioactive eicosanoids and endocannabinoids, challenges facing researchers that study them, and their roles in modulating inflammation and resolution. With a special emphasis on cystic fibrosis, a variety of therapeutics are discussed that have been explored for their potential anti-inflammatory or proresolving impact toward alleviating excessive airway inflammation and improving lung function.
气道炎症涉及募集高活性免疫细胞以对抗和清除微生物及毒性因子;然而,这种炎症反应可能会对肺组织造成意外损伤。炎症导致的组织损伤通常会通过限制炎症反应范围和持续时间的消退因子得到缓解。炎症和消退过程都需要大量脂质介质的作用,这些脂质介质可通过多种气道驻留和浸润免疫细胞快速合成。类花生酸和内源性大麻素是脂质介质的两大类,它们共享合成酶且具有多样且重叠的功能。本综述旨在总结主要的生物活性类花生酸和内源性大麻素、研究它们的研究人员面临的挑战以及它们在调节炎症和消退中的作用。特别强调囊性纤维化,讨论了已探索的多种疗法,这些疗法具有潜在的抗炎或促消退作用,可减轻过度的气道炎症并改善肺功能。