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Clinical relevance of circadian melatonin release in relapsing-remitting multiple sclerosis

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Abstract

A growing body of evidence indicates the role of melatonin (MT) in the pathogenesis of multiple sclerosis (MS): It modulates immune function, alleviates oxidative stress and it is linked to seasonality of MS relapse. This report addresses the potential clinical relevance of circadian MT rhythms in relapsing-remitting MS (RRMS) patients. The study sample comprised of fifty-five RRMS patients and fifty age- and sex-matched healthy control (HC) subjects. Circadian salivary MT was measured non-invasively at 12 time points over day in participants’ home environment. 6-Hydroxy-melatoninsulfate (MT sulfate) concentration in night-time urine was assessed as an estimate for nocturnal MT. Ratings for neurological disability, health-related quality of life (HrQoL), fatigue, depressive symptoms and sleep patterns were additionally obtained. There was no evidence for an overall disturbed MT rhythm in RRMS patients. However, lower MT levels within the first hour after awakening were associated with longer disease duration. MT levels only correlated moderately with neurological disability. Sleep disruptions were more common in patients than in controls and were associated with lower nocturnal MT sulfate levels. MT also correlated moderately with fatigue and HrQoL. We did not find evidence for a generally disturbed circadian MT rhythm in RRMS patients but longer disease duration was associated with significantly lower MT levels. Moreover, MT correlated with a series of clinical features. The exact nature of this relationship remains unclear and future studies are needed in order to determine whether MT could serve as a potential therapeutic target in MS.

Key messages

  • Melatonin acts as a free radical scavenger and modulates immune function.

  • In multiple sclerosis, low melatonin levels were associated with acute exacerbations.

  • Melatonin levels are not generally disturbed in multiple sclerosis patients.

  • But lower levels are associated with disease duration and clinical aspects.

  • Salivary melatonin after awakening might serve as a good measure of melatonin.

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Acknowledgements

We would like to thank all participants who took part in our study. We would like to thank J. Eisele for assistance (data collection).

Role of the sponsor

The funding source had no role in design, conduct of the study; collection, management, analysis, interpretation of data; preparation and review of the manuscript; decision on publication.

Funding

This study was supported by an unrestricted educational grant by Novartis Pharma GmbH, Germany.

Author information

Authors and Affiliations

  1. Zentrum für Klinische Neurowissenschaften, Klinik und Poliklinik für Neurologie, CGC Universitätsklinikum Dresden, Fetscherstr. 74, 01307, Dresden, Germany

    Simone Kern, Michael Geiger, Madlen Paucke, Alina Kästner, Katja Akgün & Tjalf Ziemssen

  2. Department of Neurology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany

    Simone Kern, Michael Geiger, Madlen Paucke, Alina Kästner, Katja Akgün & Tjalf Ziemssen

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  1. Simone Kern
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  2. Michael Geiger
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  3. Madlen Paucke
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  5. Katja Akgün
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  6. Tjalf Ziemssen
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Contributions

Dr. Kern, Dr. Paucke and Prof. Ziemssen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Dr. Kern. Acquisition of data: Dr. Paucke, Kästner, Dr. Akgün, Geiger. Analysis and interpretation of the data: Dr. Kern. Drafting of the manuscript: Dr. Kern. Critical revision of the manuscript for important intellectual content: Dr. Ziemssen, Geiger, Dr. Paucke, Kästner. Statistical analysis: Dr. Kern. Study supervision: Dr. Ziemssen, Dr. Kern, Dr. Paucke.

Corresponding author

Correspondence to Simone Kern.

Ethics declarations

Written informed consent was obtained from each participant prior to study entry. The protocol was reviewed and approved by the local ethics committee (TU Dresden, Faculty of Medicine).

Conflict of interest

Dr. Kern reports grants from Novartis Pharma GmbH, Germany during the conduct of the study; personal fees from Biogen Idec and personal fees from Teva Pharma, outside the submitted work. M. Geiger reports grants from Novartis Pharma GmbH, Germany during the conduct of the study. Dr. Paucke reports grants from Novartis Pharma GmbH, Germany during the conduct of the study. A. Kästner reports grants from Novartis Pharma GmbH during the conduct of the study. Dr. Ziemssen reports grants from Novartis Pharma GmbH, Germany during the conduct of the study; grants and personal fees from Bayer, grants and personal fees from Biogen, grants and personal fees from TEVA, grants and personal fees from Genzyme, grants and personal fees from Novartis, personal fees from Merck, personal fees from Almirall, personal fees from GSK and personal fees from Roche, outside the submitted work. Dr. Katja Akgün reports personal fee from Biogen Idec, Sanofi, Merck and Roche for oral presentations.

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Kern, S., Geiger, M., Paucke, M. et al. Clinical relevance of circadian melatonin release in relapsing-remitting multiple sclerosis. J Mol Med 97, 1547–1555 (2019). https://doi.org/10.1007/s00109-019-01821-w

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  • DOI: https://doi.org/10.1007/s00109-019-01821-w

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