Concentration of extracellular
DNA (ecDNA) in plasma of septic patients is higher in comparison to healthy controls and is associated with worse prognosis in
intensive care patients. Decrease of ecDNA in plasma by treatment with
deoxyribonuclease (
DNase) showed to have beneficial effects in animal models of
sepsis. A previously published study showed that timing of
DNase application is crucial for the effect of
DNase. No published study monitored plasma ecDNA dynamics during
sepsis in detail yet. The aim of our study was to describe the early dynamics of plasma ecDNA but also plasma
DNase activity in a mouse model of
sepsis.
Sepsis was induced using
intraperitoneal injection of E. coli and mice were euthanized every hour to obtain sufficient volume of plasma. Our results show that the concentration of plasma ecDNA is rising continuously during the first 5 h after
infection and is 20-fold higher 5 h after induction of
sepsis in comparison to control mice. Subcellular origin of plasma ecDNA was analyzed but fundamental differences in dynamics between nuclear and mitochondrial ecDNA were not found.
DNase activity in plasma seems to rise slowly until the fourth hour, but the interindividual variability is high. In conclusion, this is the first study that describes the dynamics of plasma ecDNA and
DNase activity in early
sepsis in detail. Our study is the basis for further studies focused on the timing of exogenous
DNase treatment in
sepsis. Additional studies will be needed to monitor plasma ecDNA in later time points that are more clinically relevant.