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Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.

ABSTRACT: BACKGROUND:The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti-inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental food allergy. METHODS:Balb/C mice were first sensitized with ovalbumin (OVA) in the presence of alum. Prior to oral challenges with OVA, mice were subjected to VGX or VNS. Disease severity was determined by assessing severity and onset of diarrhoea, OVA-specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis. RESULTS:When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS, on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of ?7nAChR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX3CR1hi macrophages. CONCLUSIONS:These results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune-mediated diseases.

SUBMITTER: Bosmans G

PROVIDER: S-EPMC6790670 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.

Bosmans Goele G Appeltans Iris I Stakenborg Nathalie N Gomez-Pinilla Pedro J PJ Florens Morgane V MV Aguilera-Lizarraga Javier J Matteoli Gianluca G Boeckxstaens Guy E GE

Allergy 20190415 9

<h4>Background</h4>The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti-inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental foo ...[more]

PMID: 30897213

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Project description:BackgroundAutonomic nerve stimulation is used as a treatment for a growing number of diseases. We have previously demonstrated that application of efferent vagus nerve stimulation (eVNS) has promising glucose lowering effects in a rat model of type 2 diabetes. This paradigm combines high frequency pulsatile stimulation to block nerve activation in the afferent direction with low frequency stimulation to activate the efferent nerve section. In this study we explored the effects of the parameters for nerve blocking on the ability to inhibit nerve activation in the afferent direction. The overarching aim is to establish a blocking stimulation strategy that could be applied using commercially available implantable pulse generators used in the clinic.MethodsMale rats (n = 20) had the anterior abdominal vagus nerve implanted with a multi-electrode cuff. Evoked compound action potentials (ECAP) were recorded at the proximal end of the electrode cuff. The efficacy of high frequency stimulation to block the afferent ECAP was assessed by changes in the threshold and saturation level of the response. Blocking frequency and duty cycle of the blocking pulses were varied while maintaining a constant 4 mA current amplitude.ResultsDuring application of blocking at lower frequencies (≤ 4 kHz), the ECAP threshold increased (ANOVA, p < 0.001) and saturation level decreased (p < 0.001). Application of higher duty cycles (> 70%) led to an increase in evoked neural response threshold (p < 0.001) and a decrease in saturation level (p < 0.001). During the application of a constant pulse width and frequency (1 or 1.6 kHz, > 70% duty cycle), the charge delivered per pulse had a significant influence on the magnitude of the block (ANOVA, p = 0.003), and was focal (< 2 mm range).ConclusionsThis study has determined the range of frequencies, duty cycles and currents of high frequency stimulation that generate an efficacious, focal axonal block of a predominantly C-fiber tract. These findings could have potential application for the treatment of type 2 diabetes.

Dataset Information

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.

Publications

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.

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