how tissue injury alarms the immune system and causes a systemic inflammatory response syndrome如何组织损伤警报免疫系统,引起全身炎症反应综合征.pdfVIP

Pugin Annals of Intensive Care 2012, 2:27 /content/2/1/27 REVIEW Open Access How tissue injury alarms the immune system and causes a systemic inflammatory response syndrome * Jérôme Pugin Abstract Systemic inflammation is very prevalent among critically ill patients, particularly those with extensive tissue injury. Although downstream mediators (cytokines) and effector cells (phagocytes) have been identified, proximal mediators originating from injured tissues remained elusive. Alarmins (“danger signals”) released by necrotic/injured cells have been identified recently and certainly play a role in triggering local and systemic inflammation in critically ill patients. The most promising alarmin candidates are of mitochondrial origin, i.e. mitochondrial DNA and the chemotactic factor fMet-Leu-Phe (fMLP). ATP also is released from necrotic tissues and stimulates the assembly of the inflammasome, leading to the production of proinflammatory cytokines, such as interleukin (IL)-1ß. The identification of novel alarmins opens new therapeutic avenues for the treatment of severe SIRS, and SIRS-dependent organ dysfunction. Keywords: SIRS, Inflammation, Alarmins, Danger signals, Mitochondria, Pro-inflammatory cytokines Review that SIRS may precede sepsis [4]. Because of its high Introduction prevalence in ICUs and the absence of a clear demonstra- Clinicians have recognized for a long time that critically tion of a link between clinical SIRS and systemic inflam- ill patients often present with a stress response associat- mation, some of our colleagues have proposed to abandon ing tachycardia and tachypnea, together with an “inflam-