Journal of leukocyte biology
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At the Trauma, Shock, Inflammation and Sepsis 2007 conference, the roles of complement activation products and relevant receptors were stressed in the setting of experimental sepsis [cecal ligation and puncture (CLP)] in mice and rats. In addition, some limited evidence was presented related to humans with septic shock (requiring vasopressor support). Collectively, the data suggested that events found in CLP also occur in human sepsis. ⋯ Interception in vivo of C5a or C5aR dramatically improves survival after CLP, preserves innate immune functions of blood PMNs, and greatly attenuates the intensity of consumptive coagulopathy and activation of the fibrinolytic system after CLP. In humans with septic shock, there is evidence of complement activation products in plasma along with loss of C5aRs on blood PMNs. These data suggest that in septic humans, interception of C5a or C5aR might be clinically efficacious.
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Sepsis is a systemic response to infection, and symptoms are produced by host defense systems rather than by the invading pathogens. Amongst the most prominent features of sepsis, contributing significantly to its outcome, is activation of coagulation with concurrent down-regulation of anticoagulant systems and fibrinolysis. Inflammation-induced coagulation on its turn contributes to inflammation. ⋯ Moreover, the important roles of the endothelium in down-regulating the anticoagulants TF pathway inhibitor, antithrombin, and the protein C (PC) system and inhibition of fibrinolysis are discussed. The influence of coagulation on its turn on inflammation and the endothelium is described with a special focus on protease-activated receptors (PARs). We conclude that the relationship between endothelium and coagulation in sepsis is tight and that further research is needed, for example, to better understand the role of activated PC signaling via PAR-1, the role of the endothelial PC receptor herein, and the role of the glycocalyx.
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The systemic inflammatory response observed in the setting of overwhelming infection bears striking similarities to that observed in the setting of severe traumatic injury from a clinical and physiologic standpoint. Recent observations have demonstrated that these disparate clinical entities share common mediators on a molecular level. ⋯ Evidence is accumulating that demonstrates that these mediators also play a role in the host response to tissue injury. Here, we highlight findings from the 7th World Conference on Trauma, Shock, Inflammation and Sepsis in Munich, Germany, in the context of this growing body of literature.
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Sepsis syndrome remains the leading cause of mortality in intensive care units. It is now believed that along with the body's hyperinflammatory response designated to eliminate the underlying pathogen, mechanisms are initiated to control this initial response, which can become deleterious and result in immune dysfunctions and death. A similar state of immune suppression has been described after numerous forms of severe trauma/injury. ⋯ The studies presented here support the concept that regulatory T lymphocytes (CD4+CD25+ regulatory, gammadelta, and NK T cells) play a role in the control of immune responses and are affected by injury and sepsis. This may be related to their capacity to interact with components of the innate and adaptive immune responses and to their ability to be activated nonspecifically by bacterial products and/or cytokines and to regulate through direct cell-cell and/or soluble mediators. It is our hope that a better understanding of the mechanism through which those rare lymphocyte subsets exert such a profound effect on the immune response may help in improving our ability not only to diagnose but also to treat the critically ill individual.