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 IFNγ 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.