Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Lab Anim (NY). 2019 Feb;48(2):57-65. doi: 10.1038/s41684-018-0217-2. Epub 2019 Jan 14.
Sepsis involves a disordered host response to systemic infection leading to high morbidity and mortality. Despite intense research, targeted sepsis therapies beyond antibiotics have remained elusive. The cornerstone of sepsis research is the development of animal models to mimic human bacterial infections and test novel pharmacologic targets. Nonhuman primates (NHPs) have served as an attractive, but expensive, animal to model human bacterial infections due to their nearly identical cardiopulmonary anatomy and physiology, as well as host response to infection. Several NHP species have provided substantial insight into sepsis-mediated inflammation, endothelial dysfunction, acute lung injury, and multi-organ failure. The use of NHPs has usually focused on translating therapies from early preclinical models to human clinical trials. However, despite successful sepsis interventions in NHP models, there are still no FDA-approved sepsis therapies. This review highlights major NHP models of bacterial sepsis and their relevance to clinical medicine.
败血症涉及宿主对全身感染的失调反应,导致高发病率和死亡率。尽管进行了深入研究,但除了抗生素之外,针对败血症的靶向治疗方法仍然难以捉摸。败血症研究的基石是开发动物模型来模拟人类细菌感染,并测试新的药物靶点。由于其心肺解剖和生理学以及对感染的宿主反应几乎相同,非人类灵长类动物(NHPs)成为一种有吸引力但昂贵的动物,可以模拟人类细菌感染。几种 NHP 物种为败血症介导的炎症、内皮功能障碍、急性肺损伤和多器官衰竭提供了大量的见解。NHP 的使用通常侧重于将疗法从早期临床前模型转化为人类临床试验。然而,尽管 NHP 模型中的败血症干预措施取得了成功,但仍没有获得 FDA 批准的败血症治疗方法。这篇综述重点介绍了细菌败血症的主要 NHP 模型及其与临床医学的相关性。