Sepsis and trauma remain the leading causes of morbidity and mortality. Our understanding of the molecular pathogenesis in the development of multiple organ dysfunction in sepsis and trauma has evolved as more focus is on secondary injury from innate immunity, inflammation, and the potential role of endogenous danger molecules. Studies of the past several decades have generated evidence for extracellular RNAs (exRNAs) as biologically active mediators in health and disease. Here, we review studies on plasma exRNA profiling in mice and humans with sepsis and trauma, the role and mode of action by exRNAs, such as ex-micro(mi)RNAs, in host innate immune response, and their potential implications in various organ injury during sepsis and trauma.
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