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

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. IFNgamma, TNFalpha) 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 IFNgamma (P =0.03) whereas TNFalpha 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 IFNgamma 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.