![]() ![]() In septic shock, a subgroup of sepsis characterized by profound circulatory, cellular and metabolic abnormalities, the hospital mortality rate approaches 60% ( 3).Ĭomprehensively defining “sepsis” has been subject of constant development and refinement over the last decades. ![]() Globally, mortality rates seem to be declining on average, however, up to 25% of patients still succumb to sepsis. ![]() Approximately 49 million people are affected by sepsis every year and it is estimated that 11 million deaths are caused by the syndrome, accounting for up to 19.7% of all deaths worldwide ( 2). The Third International Consensus (Sepsis-3) currently defines sepsis as “organ dysfunction caused by a dysregulated host response to infection”, emphasizing for the first time the crucial role of the innate and adaptive immune response in the development of the clinical syndrome ( 1). Sepsis is a life-threatening clinical condition with extensive physiological and biochemical abnormalities. With this review, we aim to provide an overview of sepsis immune pathophysiology, to update the choice of therapeutic approaches targeting different immunological mechanisms in the course of sepsis and septic shock, and to call for a paradigm shift from the pathogen to the host response as a potentially more promising angle. Evidence-based therapy still consists of basic causal and supportive measures, while adjuvant interventions such as blood purification or targeted immunotherapy largely remain without proof of effectiveness so far. Despite all efforts of experimental and clinical research during the last three decades, the ability to positively influence course and outcome of the syndrome remains limited. Today, the heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection, with renewed emphasis on immune pathophysiology. Sepsis is a life-threatening condition and a global disease burden. Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Dominik Jarczak Stefan Kluge Axel Nierhaus * ![]()
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