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Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?
KTH, School of Technology and Health (STH), Medical Engineering, Medical sensors, signals and systems.ORCID iD: 0000-0001-7807-8682
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2015 (English)In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients.

METHODS: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. The cytokines were then assessed after whole blood stimulation ex vivo with lipopolysaccharide (LPS) (10 and 100 ng/mL) and again in the presence of 45 and 90 μmol/L GTS-21, a cholinergic α7nAChR agonist.

RESULTS: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls. After LPS stimulation, TNF increased significantly more in patients than in controls but decreased to similar levels in both groups after addition of GTS-21. IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients. Interestingly, IL-10 increased after GTS-21 in a dose-dependent manner, but only in patients. Results in HD and PD patients did not differ.

CONCLUSIONS: The response of immune cells after LPS exposure and cholinergic stimulation suggests a functional CAP in dialysis patients. It may thus be possible to target the α7nAChR control of cytokine release as an anti-inflammatory strategy and thereby improve outcome in these patients.

Place, publisher, year, edition, pages
2015. Vol. 8, no 5
National Category
Urology and Nephrology Immunology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-179206DOI: 10.1093/ckj/sfv074PubMedID: 26413288ScopusID: 2-s2.0-84954058656OAI: oai:DiVA.org:kth-179206DiVA: diva2:881948
Note

QC 20160118

Available from: 2015-12-11 Created: 2015-12-11 Last updated: 2016-08-31Bibliographically approved
In thesis
1. Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized
Open this publication in new window or tab >>Towards Heart Rate Variability Tools in P-Health: Pervasive, Preventive, Predictive and Personalized
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.

Abstract [sv]

Hjärtfrekvensvariabilitet (HRV) har senaste tiden rönt en hel del uppmärksamhet och flera teknikerför analys av HRV i tids- resp. frekvensområdet samt medels icke-linjära metoder har utvecklats.Det har visats att HRV kan användas för att övervaka det autonoma nervsystemet (ANS) blandannat för att upptäcka särskilt vagala störningar inom ANS. Minskad HRV förknippas med flerasjukdomar såsom diabetes, reumatoid artrit, depression, kronisk hjärtsjukdom och har ävenföreslagits som prediktor för dålig prognos och plötslig hjärtdöd. HRV är dock ännu inte allmäntaccepterat som ett kliniskt verktyg utan används främst inom forskning. Framsteg inomneuroimmunitetsområdet med ökad förståelse för sambandet mellan nerv- och immunsystem, haröppnat en nytt potentiell område för HRV-applikationer. Ett exempel är när systemiskinflammationoch autoimmun sjukdom primärt orsakas av låg vagal aktivitet, vilket kan upptäckas ochprognostiseras via minskad HRV. Denna avhandling är resultatet av flera tekniska utvecklingsstegoch explorativ forskning där HRV tillämpas i syfte att utveckla ett prognostiskt diagnostiskt verktygmed förebyggande potential. Huvudsyften har varit: 1) att utveckla ett prisvärt verktyg för eneffektiv och enkel analys av HRV 2) att studera sambandet mellan HRV och pro-inflammatoriskamarkörer och därigenom potentiellt återspegla graden av aktivitet i den kolinergaantiinflammatoriska effektorvägen 3) att utveckla datorprogramvara för ett biologisktåterkopplingssystem där individen med egen träning ökar sin vagala aktivitet vilket sedanåterspeglas i en ökad HRV. I denna sammanläggningsavhandling finns utförlig beskrivning av varjeingående studies metod och resultat artikar I-VI. I ramberättelsen presenteras en kortsammanfattning av metoder och resultat, grupperade efter ämne och sammanhang.Sammanfattningsvis visar resultaten att de utvecklade verktygen adekvat registrerar och analyserarHRV korrekt enkelt , samt att HRV kan påverkas av spel-träning. HRV i framtaget koncept harpotential att användas som ett skarpt prognostiskt verktyg, inte bara för traditionell vård med fokuspå sjukdom, utan också inom friskvård. Framtagna verktyg möjliggör tidig upptäckt av minskadHRV, snabb intervention och prevention. Spelifiering med seriöst spelande utgör en potentiellplattform som motiverar en träningsrutin och som genom återkoppling kan öka HRV och därmedvälmåendet.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. 50 p.
Series
TRITA-STH : report, ISSN 1653-3836 ; 2016:5
Keyword
Heart Rate Variability, Cholinergic Anti-inflammatory Pathway, Autonomic Nervous System, Vagal activity, Biofeedback, Gamification, Serious Gaming, Inflammatory Markers, Raspberry PI
National Category
Other Medical Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-190182 (URN)978-91-7729-069-8 (ISBN)
External cooperation:
Public defence
2016-09-26, T2, Blickagången 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
VINNOVA
Note

QC 20160902

Available from: 2016-09-02 Created: 2016-08-11 Last updated: 2016-09-04Bibliographically approved

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