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Altered cytokine responses to cognitive stress in multiple sclerosis patients with fatigue

Department of Neurology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany, heesen{at}uke.uni-hamburg.de

Gabriele Koehler

Department of Neurology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

Rüdiger Gross

Department of Psychology, University of Hamburg, Hamburg, Germany

Wiebke Tessmer

Department of Neurology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

Karl-Heinz Schulz

Institute of Medical Psychology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

Stefan M Gold

Department of Neurology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany, Institute of Medical Psychology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

This study intended to examine if the immune response to a cognitive task as a variant of psychological stress in MS patients is distinct from healthy controls. The experiment was part of a larger study on mechanisms and measurements of MS fatigue. Patients (n=23) and controls (n=25) participated in a cognitive task lasting 40 minutes, in which the heart rate was continuously monitored. Blood samples were taken at baseline and directly after the stress-inducing task. Whole blood stimulated cytokine production representative of the TH-1 (i.e. IFN, TNF) and TH-2 paradigm (i.e. IL-10) was evaluated in relation to disability, fatigue, cognitive deficit, and anxiety. Patients scored high on a disease specific fatigue score compared to controls, whereas baseline cytokine patterns did not differ between the groups. MS patients displayed a blunted response of IFNg (P=0.03) whereas TNF and IL-10 responses did not change. Additionally MS patients showed a significantly lower heart rate increase after the task (P<0.001). Cognitive impairment was associated with a decreased heart rate reactivity (P=0.02) while depressive symptoms correlated with stronger IL-10 responses (P=0.05). Overall, cognitive stress induces IFN production in healthy controls but not in MS patients with fatigue. Furthermore, a reduced cardiac response might indicate an autonomic dysfunction in this group of patients.

Key Words: cognitive stress • cytokines • fatigue • multiple sclerosis • sympathetic system

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