Targeting extranuclear histones to alleviate acute and chronic inflammation

Extracellular histones instigate an inflammatory triad - centered on cytotoxicity, immune cell stimulation, and coagulation - ultimately shaping the dynamics and outcome of various inflammatory pathologies. Given the virtual absence of beneficial functions of histones in the extracellular space, in recent years a number of interference strategies have emerged. In this review we summarize pathogenic functions of extracellular histones and highlight current developments of therapeutic interference. Finally, we elaborate on the current status of preclinical attempts to interfere with extracellular histones in the context of a focus on sepsis and cardiovascular diseases, both of which are leading causes of mortality worldwide.