Stressor-Induced Alteration of Cytokine Production in Multiple Sclerosis Patients and Controls

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Abstract
We administered an acute psychological stressor to multiple sclerosis (MS) patients and normal controls to determine whether differences in subjective and physiological responses to stress may underlie the susceptibility of MS patients to stress-related exacerbations. Twenty-five MS patients (18 female, 7 male) and 25 age- and gender-matched controls participated in the study. They were asked to give a 5-minute videotaped speech defending themselves in a hypothetical scenario in which they were wrongly accused of stealing. Subjective and autonomic responses were monitored, and blood was sampled at baseline, 5, 20, and 60 minutes after the stressor to assess mitogen-stimulated production of interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). MS patients and controls demonstrated similar subjective and physiological responses to the stressor that were independent of gender, mood, and disability status. The macrophage-derived cytokines IL-1 beta and TNF-alpha were increased during the stressor, and remained elevated through 60 minutes. Th1 lymphocyte-derived IFN-gamma production also was increased at 5 and 60 minutes relative to baseline; however, there was no change in the Th2 lymphocyte-derived cytokine IL-4. These results favor the hypothesis that MS patients do not differ in stress response from normal controls; however, psychological stress may enhance cellular immune responses that would be potentially harmful to MS patients.