Abstract
Objectives: Systemic inflammatory response syndrome (SIRS) is commonly seen after sterile traumatic injury and may lead to multiple organ failure and death. Endogenous molecules termed alarmins are released following cellular stress or injury and activate the response. This literature review will discuss the mechanisms in immune system activation after trauma and compare to similar mechanisms in sepsis, with special focus on High mobility group box 1 (HMGB1). Possible future treatment options will also be briefly discussed. Methods: The review is based on (1) papers identified from search in PubMed, (2) papers received from my supervisor of the review, and (3) papers identified from citation lists from the papers after (1) and (2). Results: Activation and maintenance of the immune response after trauma and in sepsis involves the same receptors and signalling pathways, but different initial activators. Several endogenous molecules have shown alarmin characteristics both in vitro and in vivo, and preclinical studies with blockade of specific alarmins have shown promising results in reducing morbidity and mortality. Conclusion: Our understanding of mechanisms in the immune activation after trauma is insufficient, but improving. Identification of alarmins and their role in post-traumatic SIRS opens possibilities for future immune modulation also after traumatic injury, hopefully reducing the extent of inflammation, multiple organ failure, and death.
Objectives: Systemic inflammatory response syndrome (SIRS) is commonly seen after sterile traumatic injury and may lead to multiple organ failure and death. Endogenous molecules termed alarmins are released following cellular stress or injury and activate the response. This literature review will discuss the mechanisms in immune system activation after trauma and compare to similar mechanisms in sepsis, with special focus on High mobility group box 1 (HMGB1). Possible future treatment options will also be briefly discussed. Methods: The review is based on (1) papers identified from search in PubMed, (2) papers received from my supervisor of the review, and (3) papers identified from citation lists from the papers after (1) and (2). Results: Activation and maintenance of the immune response after trauma and in sepsis involves the same receptors and signalling pathways, but different initial activators. Several endogenous molecules have shown alarmin characteristics both in vitro and in vivo, and preclinical studies with blockade of specific alarmins have shown promising results in reducing morbidity and mortality. Conclusion: Our understanding of mechanisms in the immune activation after trauma is insufficient, but improving. Identification of alarmins and their role in post-traumatic SIRS opens possibilities for future immune modulation also after traumatic injury, hopefully reducing the extent of inflammation, multiple organ failure, and death.