Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.
autonomic nervous system
bioelectronic medicine
endotoxemia
inflammation
neuromodulation
specialized pro resolving mediators
splenic nerve
stimulation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
01
2021
accepted:
11
03
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
28
9
2021
Statut:
epublish
Résumé
Neuromodulation of the immune system has been proposed as a novel therapeutic strategy for the treatment of inflammatory conditions. We recently demonstrated that stimulation of near-organ autonomic nerves to the spleen can be harnessed to modulate the inflammatory response in an anesthetized pig model. The development of neuromodulation therapy for the clinic requires chronic efficacy and safety testing in a large animal model. This manuscript describes the effects of longitudinal conscious splenic nerve neuromodulation in chronically-implanted pigs. Firstly, clinically-relevant stimulation parameters were refined to efficiently activate the splenic nerve while reducing changes in cardiovascular parameters. Subsequently, pigs were implanted with a circumferential cuff electrode around the splenic neurovascular bundle connected to an implantable pulse generator, using a minimally-invasive laparoscopic procedure. Tolerability of stimulation was demonstrated in freely-behaving pigs using the refined stimulation parameters. Longitudinal stimulation significantly reduced circulating tumor necrosis factor alpha levels induced by systemic endotoxemia. This effect was accompanied by reduced peripheral monocytopenia as well as a lower systemic accumulation of CD16
Identifiants
pubmed: 33859641
doi: 10.3389/fimmu.2021.649786
pmc: PMC8043071
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
649786Informations de copyright
Copyright © 2021 Sokal, McSloy, Donegà, Kirk, Colas, Dolezalova, Gomez, Gupta, Fjordbakk, Ouchouche, Matteucci, Schlegel, Bashirullah, Werling, Harman, Rowles, Yazicioglu, Dalli, Chew and Perkins.
Déclaration de conflit d'intérêts
Authors DS, MD, IG, SO, PM, RY, KS, RB, and DC were employed by the company Galvani Bioelectronics. Author AR was employed by the company GlaxoSmithKline. Some of the work described in this publication is the subject matter of a pending patent application. AM, CF, JK, KH, JP, RC, EG, ND, and JD declare that Galvani Bioelectronics provided funds to support their work associated with this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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