α7 Nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-α production and lung injury

Kox, Matthijs; Pompe, J; Peters, Esther; Vaneker, Michiel; Laak, J.W. van der; Hoeven, Johannes G. van der; Scheffer, Gert Jan; Hoedemaekers, C.W.E.; Pickkers, Peter

doi:10.1093/bja/aer202

Cited by 66 publications

(63 citation statements)

References 40 publications

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“…Akinci et al (2) reported a deleterious effect of neostigmine in a model of endotoxemia. Moreover, Kox et al (16) reported that neostigmine had no anti-inflammatory effects on the inflammation and lung injury induced by the mechanical ventilation (MV) injury model in mice. Nevertheless, the selective pharmacological stimulation of the peripheral branch of the cholinergic antiinflammatory pathway with the selective partial ␣-7 nAChR agonist GTS-2 attenuates MV-induced TNF-␣ production at the transcriptional level and improves lung function.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the selective pharmacological stimulation of the peripheral branch of the cholinergic antiinflammatory pathway with the selective partial ␣-7 nAChR agonist GTS-2 attenuates MV-induced TNF-␣ production at the transcriptional level and improves lung function. Kox et al (16) hypothesized that the anti-inflammatory effects of GTS may be attributable to its effect on immune cells, particularly on alveolar macrophages. These data suggest the anti-inflammatory effects associated with anticholinesterase drugs depends on the drugs' pharmacological characteristics: the dose and timing of drug delivery and the tissue type involved.…”

Section: Discussionmentioning

confidence: 99%

“…The cholinergic anti-inflammatory pathway has been attracting the attention of investigators as a therapeutic strategy for protecting against myocardial ischemia reperfusion injury (7,16) and MI damage (8,9). Accumulated evidence indicates that stimulation of the efferent vagus nerve can release the important neurotransmitter ACh, which acts through the ␣-7 subunit of the nicotinic ACh receptor (␣-7 nAChR) that is expressed in macrophages and regulatory T lymphocytes (6,30,37) to modulate the anti-inflammatory response.…”

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Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

Rocha

Ribeiro

França

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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-We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4ϩ, CD8ϩ, FOXP3ϩ) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg Ϫ1 ·day Ϫ1 ) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groupsdenominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3 ϩ cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4 ϩ CD25 ϩ FOXP3 ϩ ), and a less extreme decrease in conventional T cells (CD25 ϩ FOXP3 Ϫ ) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. myocardial infarction; T lymphocytes; macrophage activation; anticholinesterase drugs; cholinergic anti-inflammatory reflex

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

Rocha

Ribeiro

França

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This approach can be obtained i) pharmacologically with α7nAChR agonists such as nicotine (Cui & Li, 2010), GTS21 (Kox et al, 2011), and AR-R17779 (van Westerloo et al, 2006), activation of the central cholinergic pathway with an AChesterase inhibitor (galantamine) (Pavlov et al, 2009) or CNI-1492, a cytokine inhibitor and synthetic guanylhydrazone mitogenactivated protein kinase blocker (Tracey, 1998), ii) high fat enteral feeding inducing the release of CCK that activates CCK1 vagal afferents thus activating the CAP (Luyer et al, 2005), iii) complementary and alternative medicines such as meditation, yoga, acupuncture, hypnosis, known to activate the VN (Keefer et al, 2013), iv) physical exercise (Mora et al, 2007), v) VNS which appears as the most interesting tool because already validated in drug resistant epilepsy and depression in human with very few side effects (Bonaz et al, 2013).…”

Section: How To Target the Vagus Nerve?mentioning

confidence: 99%

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

Bonaz

2018

Bioelectron Med

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The vagus nerve (VN), the longest nerve of the organism that innervates the gastrointestinal tract, is a mixed nerve composed of 80% of afferent and 20% of efferent fibers. The VN has anti-inflammatory properties, in particular an anti-TNFα effect through the cholinergic anti-inflammatory pathway. The VN is a key component of the autonomic nervous system, i.e. the parasympathetic nervous system. An imbalance of the autonomic nervous system, as represented by a low vagal tone, is described in many diseases and has a pro-inflammatory role. Inflammatory bowel diseases (IBD) are chronic disorders of the gastro-intestinal tract where TNFα is a key cytokine. VN stimulation (VNS), classically used for the treatment of drug resistant epilepsy and depression, would be of interest in the treatment of IBD. We have recently reported in a 6 month follow-up pilot study that VNS improves active Crohn's disease. Preliminary data of another pilot study confirm this interest. Similarly, VNS has recently been reported to improve rheumatoid arthritis, another TNFα mediated disease. Bioelectronic Medicine, as represented by VNS, opens new therapeutic avenues in the treatment of such chronic inflammatory disorders. In the present manuscript, we will focus on the interest of VNS in IBD.

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“…Like other inhibitors of AChE, galantamine causes better availability of the neurotransmitter acetylcholine not only in central nervous system, but also in the other parts of cholinergic nerves. Cholinergic anti-infl ammatory pathway is one of the crucial parts of the nerves having acetylcholine as a neurotransmitter and is involved in neuronal control over immunity (6)(7)(8)(9). Though the most common way how to initiate cholinergic anti-infl ammatory pathway is by application of an agonist on nAChR, inhibitors of AChE appears also as potent stimulants of the pathway.…”

Section: Introductionmentioning

confidence: 99%

Galantamine has impact on immunity in mice exposed to keyhole limpet hemocyanin

Pohanka¹,

Zakova²,

Fusek³

2017

BLL

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OBJECTIVES: In this work, we hypothesized whether galantamine could interact with the cholinergic anti-infl ammatory pathway and modulate immunity this way. BACKGROUND: Galantamine is a drug used for the therapy of Alzheimer disease. The drug inhibits enzyme acetylcholinesterase in the central nervous system, which causes better availability of neurotransmitter acetylcholine. METHODS: In the experiment, we immunized BALB/c laboratory mice by keyhole limpet hemocyanin (KLH) in combination with galantamine in a dose 0.02-0.5 mg/kg. The animals were sacrifi ced from 1 to 7 days after the substances applications and plasma was collected in order to examine immunochemical markers by enzymelinked immunosorbent assay. RESULTS: We found signifi cant drop in production of immunoglobulins and interleukin (IL) 4 level while IL2, IL4 and tumour necrosis factor α remained unaltered for the whole experiment. We infer that galantamine causes better availability of acetylcholine also in blood system, where the neurotransmitter interacts with nicotinic acetylcholine receptors on macrophages and initiates cholinergic anti-infl ammatory pathway. CONCLUSIONS: In a conclusion, galantamine can cause lower effi cacy of vaccination or immunity response to an infectious disease and the phenomenon should be taken into consideration in the current therapy (Tab. 1, Fig. 2, Ref. 24). Text in PDF www.elis.sk.

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α7 Nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-α production and lung injury

Cited by 66 publications

References 40 publications

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

Galantamine has impact on immunity in mice exposed to keyhole limpet hemocyanin

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