An ongoing search for potential targets and therapies for lethal sepsis.
An ongoing search for potential targets and therapies for lethal sepsis.
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DOI：
10.1186/s40779-015-0047-0
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发表时间：
2015
影响因子：
21.1
通讯作者：
Wang HC
中科院分区：
文献类型：
--
作者：
Bao GQ;He L;Lee D;D'Angelo J;Wang HC
脓毒症是指由微生物感染引起的全身炎症反应综合征，是重症监护病房死亡的主要原因。脓毒症的发病机制仍然知之甚少，尽管它可归因于先天免疫细胞协调的免疫反应失调，这些细胞依次释放早期（例如肿瘤坏死因子（TNF）、白细胞介素-1（IL-1）和干扰素-γ（IFN-γ））和晚期（例如高迁移率族蛋白1（HMGB1））促炎介质。作为一种普遍存在的核蛋白，HMGB1 可以从病理损伤的细胞中被动释放，从而将感染和损伤归咎于通常失调的炎症反应。我们回顾了支持细胞外 HMGB1 作为炎症性疾病晚期介质的证据，并讨论了几种中草药成分作为 HMGB1 靶向疗法的潜力。我们认为，在脓毒症和其他炎症性疾病的临床治疗中，制定特异性减弱损伤引起的炎症反应而不损害感染介导的先天免疫的策略非常重要。
Sepsis, which refers to a systemic inflammatory response syndrome resulting from a microbial infection, represents the leading cause of death in intensive care units. The pathogenesis of sepsis remains poorly understood although it is attributable to dysregulated immune responses orchestrated by innate immune cells that are sequentially released early (e.g., tumor necrosis factor(TNF), interleukin-1(IL-1), and interferon-γ(IFN-γ)) and late (e.g., high mobility group box 1(HMGB1)) pro-inflammatory mediators. As a ubiquitous nuclear protein, HMGB1 can be passively released from pathologically damaged cells, thereby converging infection and injury on commonly dysregulated inflammatory responses. We review evidence that supports extracellular HMGB1 as a late mediator of inflammatory diseases and discuss the potential of several Chinese herbal components as HMGB1-targeting therapies. We propose that it is important to develop strategies for specifically attenuating injury-elicited inflammatory responses without compromising the infection-mediated innate immunity for the clinical management of sepsis and other inflammatory diseases.