Impact of sepsis on circulating exosomes: pathophysiological mechanisms, biomarker potential, and therapeutic applications

This comprehensive review examines the complex interplay between sepsis and circulating exosomes. Sepsis, characterized by dysregulated host response to infection leading to life-threatening organ dysfunction, remains a significant global health challenge with high mortality rates. Exosomes, small extracellular vesicles (30-150 nm) released by most cell types, play crucial roles in intercellular communication by transferring bioactive molecules. During sepsis, both exosome quantity and cargo composition undergo significant alterations, reflecting the host's pathophysiological state. The review explores how sepsis-induced inflammation influences exosome biogenesis and content, including proteins, microRNAs, and other non-coding RNAs. These modified exosomes can propagate inflammatory signals throughout the body while also participating in immunosuppressive mechanisms characteristic of later sepsis stages. The potential of exosomes as diagnostic and prognostic biomarkers is highlighted, with specific exosomal components correlating with disease severity and organ dysfunction. Additionally, emerging therapeutic strategies targeting exosomes or utilizing them as delivery vehicles for anti-inflammatory agents are discussed. By consolidating recent findings, this review underscores the significance of exosome research in advancing our understanding of sepsis pathophysiology and developing novel interventions for this complex syndrome.