The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation
Abstract Background Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Place...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Molecular Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s10020-019-0097-y |
| _version_ | 1828764056362680320 |
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| author | Marie Hilderman Abdul Rashid Qureshi Farhad Abtahi Nils Witt Christina Jägren Joakim Olbers Martin Delle Kaj Lindecrantz Annette Bruchfeld |
| author_facet | Marie Hilderman Abdul Rashid Qureshi Farhad Abtahi Nils Witt Christina Jägren Joakim Olbers Martin Delle Kaj Lindecrantz Annette Bruchfeld |
| author_sort | Marie Hilderman |
| collection | DOAJ |
| description | Abstract Background Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF. Methods Ten patients treated with RDN (St Jude EnligHTN™), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC). Results Baseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up. Conclusion RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation. |
| first_indexed | 2024-12-11T02:13:43Z |
| format | Article |
| id | doaj.art-ed40f5fe53bc494b876ba112e27bd3d0 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-11T02:13:43Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-ed40f5fe53bc494b876ba112e27bd3d02022-12-22T01:24:14ZengBMCMolecular Medicine1076-15511528-36582019-08-0125111010.1186/s10020-019-0097-yThe cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervationMarie Hilderman0Abdul Rashid Qureshi1Farhad Abtahi2Nils Witt3Christina Jägren4Joakim Olbers5Martin Delle6Kaj Lindecrantz7Annette Bruchfeld8Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska InstitutetDepartment of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska InstitutetInstitute of Environmental Medicine, Division of Occupational Medicine, Karolinska InstitutetDepartment of Clinical Science and Education, Division of Cardiology, Karolinska Insititutet, SödersjukhusetDepartment of Clinical Science and Education, Division of Cardiology, Karolinska Insititutet, SödersjukhusetDepartment of Clinical Science and Education, Division of Cardiology, Karolinska Insititutet, SödersjukhusetDepartment of Radiology, Interventional Radiology, Karolinska University HospitalInstitute of Environmental Medicine, Division of Occupational Medicine, Karolinska InstitutetDepartment of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska InstitutetAbstract Background Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF. Methods Ten patients treated with RDN (St Jude EnligHTN™), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC). Results Baseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up. Conclusion RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.http://link.springer.com/article/10.1186/s10020-019-0097-yResistant hypertensionCholinergic anti-inflammatory pathwayRenal denervationInflammationPlacental growth factor |
| spellingShingle | Marie Hilderman Abdul Rashid Qureshi Farhad Abtahi Nils Witt Christina Jägren Joakim Olbers Martin Delle Kaj Lindecrantz Annette Bruchfeld The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation Molecular Medicine Resistant hypertension Cholinergic anti-inflammatory pathway Renal denervation Inflammation Placental growth factor |
| title | The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation |
| title_full | The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation |
| title_fullStr | The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation |
| title_full_unstemmed | The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation |
| title_short | The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation |
| title_sort | cholinergic anti inflammatory pathway in resistant hypertension treated with renal denervation |
| topic | Resistant hypertension Cholinergic anti-inflammatory pathway Renal denervation Inflammation Placental growth factor |
| url | http://link.springer.com/article/10.1186/s10020-019-0097-y |
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