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Disease Markers
Volume 2015, Article ID 758314, 7 pages
Clinical Study

Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?

1Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands
2MS Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands
3Department of Rehabilitation Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands
4EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands

Received 22 September 2014; Revised 9 December 2014; Accepted 9 December 2014

Academic Editor: Mariann Harangi

Copyright © 2015 Arjan Malekzadeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue 34) and fatigued (CIS20r fatigue 35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with and without fatigue . Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628.