Fatigue in patients with multiple sclerosis: is it related to pro- and anti-inflammatory cytokines?
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 (n = 21) and without fatigue (n = 14). 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.


CONCLUSIONS
The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS.


BACKGROUND
ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628.
Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; MS Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
Arjan
A
Malekzadeh
Department of Rehabilitation Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
Wietske
W
Van de Geer-Peeters
MS Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; Department of Rehabilitation Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
Vincent
V
De Groot
Neurochemistry Laboratory, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; MS Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
Charlotte Elisabeth
CE
Teunissen
MS Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; Department of Rehabilitation Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands ; EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
Heleen
H
Beckerman
Department of Rehabilitation Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands.
D000293:Adolescent; D000328:Adult; D000368:Aged; D005221:Fatigue / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma