Auricular Vagus Nerve Stimulation Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Neutrophil Infiltration and Neutrophil Extracellular Traps Formation

Vagus nerve stimulation has been shown to exert anti-inflammation activities in sepsis. However, surgical implantation of stimulation devices is performed under general anesthesia, which limits its clinical application. Auricular vagus nerve stimulation (AVNS) is a minimal invasive technique that delivers electrical currents to the auricular branch of the vagus nerve. The purpose of this study was to determine the effects of AVNS on systemic inflammation, lung injury, neutrophil infiltration, and neutrophil extracellular traps (NETs) formation in the lung. In a LPS challenge lung-injury mice model, AVNS was applied to bilateral ears. Twelve hours after LPS administration, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. We found that the treatment with AVNS significantly attenuated histopathological changes and neutrophil infiltration in the lung tissue, inhibited inflammatory cytokine elevations in serum and BALF, and decreased protein concentrations in BALF. Besides, AVNS decreased leukocyte and neutrophil accounts in BALF. Furthermore, colocalization of citrullination of histone H3 and myeloperoxidase expressions (highly specific marker of NETs) was reduced in AVNS mice. In conclusion, AVNS reduced systemic inflammation, attenuated lung edema, and inhibited neutrophil infiltration and NETs formation in the lung in LPS mice.