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Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study

May, Shaun M; Chiang, Eric; Reyes, Anna; Martir, Gladys; Patel, Amour; Karmali, Shamir; Patel, Sanjiv; ... Ackland, Gareth L; + view all (2021) Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study. Brain, Behavior, & Immunity - Health , 16 , Article 100299. 10.1016/j.bbih.2021.100299. Green open access

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Abstract

Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical β2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 ​± ​19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 ​× ​8 min cycles of brachial artery occlusion using a blood pressure cuff (RICblock). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 ​min after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 ​ms (95% confidence intervals (95%CI):13-66; n ​= ​17 subjects; P ​= ​0.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 ​ms (95%CI:-11 to 50); P ​= ​0.19). The high-frequency component of HRV was reduced after RICblock, but remained unchanged after RIC (P ​< ​0.001), indicating that RIC preserved vagal activity. LPS-induced CD16+CD11b+ expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RICblock. These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC.

Type: Article
Title: Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbih.2021.100299
Publisher version: https://doi.org/10.1016/j.bbih.2021.100299
Language: English
Additional information: © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Autonomic nervous system, Heart rate variability, Inflammation, Neutrophil, Remote ischaemic conditioning, Vagus
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10144430
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