Author: Caroline Sévoz-Couche1,2, Wupeng Liao2,3, Hazel Y C Foo2,3, Isabelle Bonne4,5, Thong Beng Lu4,5, Caris Tan Qi Hui6, Wendy Yen Xian Peh7,8, Shi-Cheng Yen7,8, W S Fred Wong2,3,9
Affiliation:
1 INSERM, UMRS1158 Neurophysiologie Respiratoire et Clinique, Sorbonne Université, Paris, France.
2 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
3 Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, Singapore.
4 Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5 Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
6 Advanced imaging and Histology Core, Immunology Program, Life Science Institute, National University of Singapore, Singapore.
7 The N.1 Institute for Health, National University of Singapore, Singapore.
8 Department of Electrical and Computer Engineering, National University of Singapore, Singapore.
9 Drug Discovery and Optimization Platform, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Conference/Journal: Br J Pharmacol
Date published: 2024 Mar 2
Other:
Special Notes: doi: 10.1111/bph.16334. , Word Count: 246
Background and purpose:
Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti-inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)-induced CAP on allergic inflammation remain unknown.
Experimental approach:
BALB/c mice were sensitized and challenged with house dust mite (HDM) extract and treated with active VNS (5 Hz, 0.5 ms, 0.05-1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy.
Key results:
In the HDM mouse asthma model, VNS at intensities equal to or above 0.1 mA (VNS 0.1) but not sham VNS reduced BAL fluid differential cell counts and alveolar macrophages expressing α7 nicotinic receptors (α7nAChR), goblet cell hyperplasia, and collagen deposition. Besides, VNS 0.1 also abated HDM-induced elevation of type 2 cytokines IL-4 and IL-5 and was found to block the phosphorylation of transcription factor STAT6 and expression level of IRF4 in total lung lysates. Finally, VNS 0.1 abrogated methacholine-induced hyperresponsiveness in asthma mice. Prior administration of α-bungarotoxin, a specific inhibitor of α7nAChR, but not propranolol, a specific inhibitor of β2-adrenoceptors, abolished the therapeutic effects of VNS 0.1.
Conclusion and implications:
Our data revealed the protective effects of VNS on various clinical features in allergic airway inflammation model. VNS, a clinically approved therapy for depression and epilepsy, appears to be a promising new strategy for controlling allergic asthma.
Keywords: asthma; bronchoalveolar inflammation; nicotinic receptors; vagus nerve stimulation.
PMID: 38430056 DOI: 10.1111/bph.16334
