Propofol Inhibits Neutrophil Extracellular Traps Formation and Alleviates Sepsis-Induced Acute Lung Injury.

BACKGROUND

Excessive neutrophil extracellular traps (NETs) formation contributes to lung tissue injury in sepsis-associated acute lung injury (ALI). Propofol, a commonly used sedative with anti-inflammatory and antioxidant properties, has been suggested to confer protection against ALI; however, its effects on NET sformation and the underlying mechanisms remain poorly defined.

METHODS AND

RESULTS

At the cellular level, we established an in vitro model of lipopolysaccharide (LPS)-induced NET formation using human peripheral blood neutrophils to evaluate the effects of propofol. Pharmacological inhibition experiments in vitro suggested that propofol may suppress NET release by modulating Akt/mTOR signaling, with a concomitant reduction in neutrophil autophagic activity. In parallel, we established an LPS-induced sepsis model in mice and administered propofol by intraperitoneal pretreatment. Lung histopathology and NET quantification showed that propofol treatment was associated with attenuated sepsis‑induced lung injury and suppressed NET formation in vivo. These protective effects were associated with increased Akt/mTOR pathway activity in lung tissue; however, because in vivo pathway blockade was not performed, the functional contribution of Akt/mTOR signaling to organ protection in this setting remains to be directly validated.

CONCLUSIONS

Propofol attenuates sepsis-induced lung injury in association with suppressed NET formation. In vitro pharmacological inhibition experiments suggest that the Akt/mTOR axis may represent one pathway through which propofol suppresses NET release. However, direct in vivo validation of this mechanism (e.g., using pathway-specific inhibitors, conditional knockout models, or other loss-of-function approaches) remains necessary and should be addressed in future studies. Collectively, these findings identify a previously underappreciated mechanism of propofol action and support its potential adjunctive role in sepsis management.