title: An ongoing search for potential targets and therapies for lethal sepsis.
abstract: 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.
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030 USA.|The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030 USA.|Department of General Surgery, Tangdu Hospital, The 4th Military Medical University, Xi'an, Shaanxi 710032 China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Bao
authors.affiliation: Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030 USA.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030 USA.
authors.forename: John
authors.initials: J
authors.lastname: D'Angelo
authors.affiliation: Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030 USA.|The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030 USA.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Wang
keywords: Autophagy; Double-stranded RNA-activated protein kinase R; Endocytosis; Herbal components; High mobility group box 1; Innate immune cells; Pathogen-associated molecular pattern molecules; Sepsis