The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Expert Opin Ther Targets. 2023 Jul-Dec;27(7):575-591. doi: 10.1080/14728222.2023.2239495. Epub 2023 Jul 25.
Microbial infections and resultant sepsis are leading causes of death in hospitals, representing approximately 20% of total deaths worldwide. Despite the difficulties in translating experimental insights into effective therapies for often heterogenous patient populations, an improved understanding of the pathogenic mechanisms underlying experimental sepsis is still urgently needed. Sepsis is partly attributable to dysregulated innate immune responses manifested by hyperinflammation and immunosuppression at different stages of microbial infections.
Here we review our recent progress in searching for late-acting mediators of experimental sepsis and propose high mobility group box 1 (HMGB1) and procathepsin-L (pCTS-L) as potential therapeutic targets for improving outcomes of lethal sepsis and other infectious diseases.
It will be important to evaluate the efficacy of HMGB1- or pCTS-L-targeting agents for the clinical management of human sepsis and other infectious diseases in future studies.
微生物感染和由此导致的败血症是医院内死亡的主要原因，约占全球总死亡人数的 20%。尽管将实验见解转化为针对异质患者群体的有效治疗方法存在困难，但仍迫切需要更好地了解实验性败血症的发病机制。败血症部分归因于先天免疫反应失调，在微生物感染的不同阶段表现为过度炎症和免疫抑制。
在这里，我们回顾了我们在寻找实验性败血症晚期作用介质方面的最新进展，并提出高迁移率族蛋白 B1（HMGB1）和组织蛋白酶-L 前体（pCTS-L）作为改善致死性败血症和其他传染病结局的潜在治疗靶点。
在未来的研究中，评估针对 HMGB1 或 pCTS-L 的靶向药物对人类败血症和其他传染病的临床管理的疗效将是重要的。
