Extracellular histones, normally nuclear proteins essential for chromatin structure, play a harmful role when released into circulation during cell death processes like NETosis.

Acting as damage-associated molecular patterns (DAMPs), they drive excessive inflammation, disrupt endothelial function, alter immune responses, trigger coagulation, and cause cell and organ damage.

Their involvement has been linked to severe conditions such as sepsis, acute lung and cardiac injuries, and pancreatitis.

Due to their strong association with disease severity and outcomes, circulating histones are being explored as valuable biomarkers for diagnosis, prognosis, and therapy monitoring in critically ill patients. Current research also focuses on strategies to detect, neutralize, or remove these histones to improve clinical outcomes.