Departments of Pediatrics, Ophthalmology and Pharmacology, CHU Sainte-Justine Research Center, Montreal, H3T 1C5, Canada.
Department of Pharmacology, Universite de Montreal, Montreal, H3T 1J4, Canada.
Curr Pharm Des. 2017;23(40):6132-6141. doi: 10.2174/1381612823666170825145114.
Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and surviving infants are at increased risks of lifelong complications. PTB has been firmly linked to inflammation regardless of infection, specific aetiology or timing of birth. Deleterious inflammation is observed in maternal and fetal tissue, and correlates with the severity of perinatal complications. At present, PTB is treated with tocolytics as though it is exclusively a myometrial contractile disorder. These agents do not address underlying inflammatory processes and are thus vastly ineffective at improving neonatal outcomes. Of all inflammatory mediators, IL-1 is central to the pathophysiology of PTB and most adverse neonatal outcomes. We thus present herein a review of the various effects of IL-1 in utero, with a brief overview of its mechanism of action. We then discuss the potential of different IL-1-targeting agents based on pre-clinical testing in relevant models of PTB and neonatal inflammatory injuries.
早产(PTB)是全球新生儿死亡和发病的主要原因,存活的婴儿有终生并发症的风险增加。无论是否存在感染、特定病因或分娩时间,早产都与炎症密切相关。有害炎症在母体和胎儿组织中观察到,并与围产期并发症的严重程度相关。目前,PTB 的治疗方法是使用宫缩抑制剂,就好像它仅仅是一种子宫收缩障碍。这些药物不能解决潜在的炎症过程,因此在改善新生儿结局方面效果非常有限。在所有的炎症介质中,IL-1 在 PTB 的病理生理学和大多数不良新生儿结局中起核心作用。因此,本文综述了 IL-1 在子宫内的各种作用,并简要概述了其作用机制。然后,我们讨论了基于 PTB 和新生儿炎症损伤相关模型的临床前试验中不同 IL-1 靶向药物的潜力。