Vagus Nerve Stimulation Decreases Pancreatitis Severity In Mice

Background: Vagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP).Methods: Two independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-alpha levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of alpha 7nAChR(+) macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned alpha 7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS.Results: VNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-alpha and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of alpha 7nAChR(+) macrophages in pancreas and spleen. Adoptive transfer of VNS-treated alpha 7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS.Conclusions: VNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to alpha 7nAChR on macrophage.