J Manson1, C Thiemermann, K Brohi. 1. Trauma Sciences, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. joanna.manson@gmail.com
Abstract
BACKGROUND: A systemic inflammatory response syndrome (SIRS) is frequently observed after traumatic injury. The response is sterile and the activating stimulus is tissue damage. Endogenous molecules, called alarmins, are reputed to be released by injured tissues but the precise identity of these mediators is unclear. This review summarizes current preclinical and clinical evidence for trauma alarmins and their role in innate immune activation. METHODS: A comprehensive literature review of putative alarmins in tissue damage after traumatic injury was conducted. RESULTS: The presence of SIRS at admission is an independent predictor of mortality after trauma. The primary initiators of the human immune response are unclear. Several endogenous substances display alarmin characteristics in vitro. Preclinical studies demonstrate that blockade of certain endogenous substances can reduce adverse clinical sequelae after traumatic injury. Human evidence for trauma alarmins is extremely limited. CONCLUSION: The magnitude of acute inflammation is predictive of outcome after trauma, suggesting that an early opportunity for immune modulation may exist. An understanding of the mechanisms of innate immune activation following trauma may lead to new therapeutic agents and improved patient survival.
BACKGROUND: A systemic inflammatory response syndrome (SIRS) is frequently observed after traumatic injury. The response is sterile and the activating stimulus is tissue damage. Endogenous molecules, called alarmins, are reputed to be released by injured tissues but the precise identity of these mediators is unclear. This review summarizes current preclinical and clinical evidence for trauma alarmins and their role in innate immune activation. METHODS: A comprehensive literature review of putative alarmins in tissue damage after traumatic injury was conducted. RESULTS: The presence of SIRS at admission is an independent predictor of mortality after trauma. The primary initiators of the human immune response are unclear. Several endogenous substances display alarmin characteristics in vitro. Preclinical studies demonstrate that blockade of certain endogenous substances can reduce adverse clinical sequelae after traumatic injury. Human evidence for trauma alarmins is extremely limited. CONCLUSION: The magnitude of acute inflammation is predictive of outcome after trauma, suggesting that an early opportunity for immune modulation may exist. An understanding of the mechanisms of innate immune activation following trauma may lead to new therapeutic agents and improved patient survival.
Authors: Elliot J Glotfelty; Thomas Delgado; Luis B Tovar-Y-Romo; Yu Luo; Barry Hoffer; Lars Olson; Tobias Karlsson; Mark P Mattson; Brandon Harvey; David Tweedie; Yazhou Li; Nigel H Greig Journal: ACS Pharmacol Transl Sci Date: 2019-02-11