Fatigue and interleukin-6

Malekzadeh A, Van de Geer-Peeters W, De Groot V, Elisabeth Teunissen C, Beckerman H, Trefams-Ace Study Group. Fatigue in patients with multiple sclerosis: is it related to pro- and anti-inflammatory cytokines? Dis Markers. 2015;2015:758314. 

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. 
Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS.
Fatigue is one of the troubling symptoms and this study attempts to link this to blood levels of interleukin-6 (IL-6). Blocking inflammation can limit fatigue, what this suggests is that IL-6 may be part of the problem, but blood levels of cytokines can be misleading, are they there because they are surplus to requirements?, otherwise they should be bound to their targets. Blockage of  Interleukin-6 is being studied in NMO does this do anything to Fatigue.

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