THE ROLES OF EXTRACELLULAR VESICLES IN SEPSIS AND SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

Sepsis is a life-threatening organ dysfunction, caused by dysregulation of the host response to infection. To understand the underlying mechanisms of sepsis, the vast spectrum of extracellular vesicles (EVs) is gaining importance in this research field. A connection between EVs and sepsis was shown in 1998 in an endotoxemia pig model. Since then, the number of studies describing EVs as markers and mediators of sepsis increased steadily. Extracellular vesicles in sepsis could be friends and foes at the same time depending on their origin and cargo. On the one hand, transfer of EVs or outer membrane vesicles can induce sepsis or systemic inflammatory response syndrome with comparable efficiency as well-established methods, such as cecal ligation puncture or lipopolysaccharide injection. On the other hand, EVs could provide certain therapeutic effects, mediated via reduction of reactive oxygen species, inflammatory cytokines and chemokines, influence on macrophage polarization and apoptosis, as well as increase of anti-inflammatory cytokines. Moreover, EVs could be helpful in the diagnosis of sepsis. Extracellular vesicles of different cellular origin, such as leucocytes, macrophages, platelets, and granulocytes, have been suggested as potential sepsis biomarkers. They ensure the diagnosis of sepsis earlier than classical clinical inflammation markers, such as C-reactive protein, leucocytes, or IL-6. This review summarizes the three roles of EVs in sepsis—mediator/inducer, biomarker, and therapeutic tool.