Vagal Afferent Stimulation Attenuates LPS-Induced Acute Lung Inflammation in Association with Reduced Spleen Weight...

Vagal afferent stimulation exerts potent anti-inflammatory effects through neuroimmune pathways involving the sympathetic nervous system and spleen. However, how vagal afferent stimulation affects splenic responses and CellTrace-positive signals in inflamed tissues remains unclear. In this study, we investigated the effects of vagal afferent electrical stimulation (aVNS) on splenic responses and acute lung inflammation induced by intratracheal lipopolysaccharide (LPS) in mice. As a preconditioning intervention, aVNS was applied to the right cervical vagus nerve 24 h before LPS administration. Pulmonary inflammation was evaluated by measuring tumor necrosis factor-α (TNF-α) levels in bronchoalveolar lavage fluid. Splenic responses were assessed by measuring spleen weight, and CellTrace-positive signals were evaluated following direct intrasplenic injection of CellTrace™ Far Red. aVNS significantly reduced BALF TNF-α levels (sham: 5443 ± 404 pg/mL, n = 5; aVNS: 2891 ± 756 pg/mL, n = 5) following LPS administration. In addition, aVNS reduced spleen weight 24 h after stimulation. Furthermore, the ratio of CellTrace Far Red-positive cells was significantly higher in the aVNS + LPS group than in the sham + LPS group (0.00504 ± 0.00056 vs. 0.00151 ± 0.00017, n = 4 per group). These findings indicate that vagal afferent stimulation reduces the BALF TNF-α response to LPS and is associated with reduced spleen weight and increased CellTrace-positive objects detected in lung sections. These observations suggest that changes in splenic and immune-cell dynamics may accompany the anti-inflammatory effects of vagal afferent stimulation.