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Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the search of biomarkers in multiple sclerosis

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Abstract

Inflammatory serum parameters are intensely investigated in the search of biomarkers for disease activity and treatment response in multiple sclerosis (MS). A reason for contradictory results might be the timing of blood collection for analyzing serum concentrations of inflammatory parameters which are subject to diurnal changes. We included 34 untreated patients with relapsing-remitting MS and 34 age- and sex-matched healthy controls. 12 MS patients showed acute disease activity in corresponding MRI scans. Blood samples were obtained at 7.00, 11.00 am, 2.30, 6.00 and 9.30 pm within 1 day. We determined serum levels of cortisol and inflammatory markers including soluble tumor necrosis factor-beta (sTNF-β), soluble TNF-Receptor-1 (sTNF-R1) and -2 (sTNF-2), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) by ELISA. We observed significantly higher serum levels of sTNF-R1 (p < 0.001) and sTNF-R2 (p < 0.001) in the morning and a significant decline of sICAM-1 (p < 0.005) and sVCAM-1 (p < 0.001) in the afternoon in both, MS patients and healthy controls. Comparison of diurnal serum levels between MS patients with active versus with non-active disease revealed significantly higher serum levels of sVCAM-1 (p < 0.05) around noon and in the early afternoon in MS patients with active disease. A significant decline of sICAM-1 (p < 0.05) in the afternoon was seen in MS patients with active and non-active disease. Our data indicate that increased awareness of potential diurnal serum concentration changes of biomarkers can eliminate one major cause of biased data as they occur in most of the investigated immunological parameters.

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Conflicts of interest

We certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Ethical standard

This study has been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University and Salzburger Landeskliniken, Ignaz-Harrer-Straße 79, 5020, Salzburg, Austria

    P. Wipfler, A. Harrer, G. Pilz, A. Kunz, S. M. Golaszewski & J. Kraus

  2. Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Am Steg 14, 35385, Giessen, Germany

    A. Heikkinen, R. Reuss & Patrick Oschmann

  3. Department of Neurology, Hospital Hohe Warte, Hohe Warte 8, 95445, Bayreuth, Germany

    R. Reuss & Patrick Oschmann

  4. Neurologische Klinik der Klinikum Bayreuth GmbH, Hohe Warte 8, 95445, Bayreuth, Germany

    Patrick Oschmann

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  1. P. Wipfler
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  2. A. Heikkinen
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  3. A. Harrer
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  4. G. Pilz
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  5. A. Kunz
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  6. S. M. Golaszewski
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  7. R. Reuss
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  8. Patrick Oschmann
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  9. J. Kraus
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Corresponding author

Correspondence to Patrick Oschmann.

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Wipfler, P., Heikkinen, A., Harrer, A. et al. Circadian rhythmicity of inflammatory serum parameters: a neglected issue in the search of biomarkers in multiple sclerosis. J Neurol 260, 221–227 (2013). https://doi.org/10.1007/s00415-012-6622-3

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  • DOI: https://doi.org/10.1007/s00415-012-6622-3

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