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. 2012 Jul 12;2(1):27.
doi: 10.1186/2110-5820-2-27.

How tissue injury alarms the immune system and causes a systemic inflammatory response syndrome

Jérôme Pugin  1
Affiliations

How tissue injury alarms the immune system and causes a systemic inflammatory response syndrome

Jérôme Pugin. Ann Intensive Care. .

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.

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Figures

Figure 1
Figure 1
Inflammation induced by alarmins released from injured/necrotic cells.A. Injured/necrotic cells with membrane breaks release ATP and mitochondrial alarmins (mitochondrial products). B. Extracellular ATP stimulates in target (immune) cells the assembly of the NALP3 inflammasome via its interaction with the P2X7 receptor, activating caspase-1. Mitochondrial (mt)DNA stimulates the transcription of the pro-IL-1ß gene via its interaction with TLR9 receptor, and the production of pro-IL-1ß that will be cleaved by activated caspase-1 into bioactive IL-1ß, which in turn can be released into the alveolar space and the interstitium and generate local inflammation. fMLP will create chemotactic gradients to attract neutrophils to the injured tissues. C. Neutrophils attracted to the injured tissues will be activated further by fMLP and IL-1ß via their respective receptors (FPR1, and IL-1R), generate oxidative burst and release proteases, which could be further deleterious to tissues (neutrophil-dependent tissue injury).
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References

    1. Bone RC. Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome) JAMA. 1992;268:3452–3455. doi: 10.1001/jama.1992.03490240060037. - DOI - PubMed
    1. Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest. 1992;101:1481–1483. doi: 10.1378/chest.101.6.1481. - DOI - PubMed
    1. Pittet D, Rangel-Frausto S, Li N. et al.Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients. Intensive Care Med. 1995;21:302–309. doi: 10.1007/BF01705408. - DOI - PubMed
    1. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS) A prospective study. JAMA. 1995;273:117–123. doi: 10.1001/jama.1995.03520260039030. - DOI - PubMed
    1. Dear VJL. SIRS I'm sorry to say that I don't like you. Crit Care Med. 1997;25:372–374. doi: 10.1097/00003246-199702000-00029. - DOI - PubMed

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