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.
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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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