Background: Fatigue is one of the most common disabling symptoms in patients with multiple sclerosis (MS), but the putative role of proinflammatory cytokines remains to be elucidated. Methods: Thirty-seven patients (27 women, 10 men) with relapsing-remitting (n =29) and secondary progressive (n =8) MS, aged 41.0 ± 10.2 years, were studied. Fatigue was assessed by Krupp’s Fatigue Severity Scale (FSS). C ytokine mRNA expression for interferon (IFN)-g, tumor necro sis factor (TNF)-a and interleukin (IL)-10 were measured by real time RT PC R. A utonomic function was evaluated by standard tests for parasympathetic and sympathetic function, as well as by serum levels of norepinephrine and epinephrine. Results: Median levels of TNF-a mRNA expression were significantly higher in MS patients with (FSS]-4.0 and]-5.0, n=26 and n=14, respectively) than in those without fatigue (FSSB-4.0, n =11). No differences were seen for IFN-g and IL-10 mRNA expression. C ytokine levels were not correlated to autonomic tests or to serum catecho lamine levels. Conclusions: These results suggest that TNF-a, as a principal proinflammatory mediator, is associated with MS-related fatigue. This is in support of a patho genic role of the MS-related inflammatory process in the development of fatigue.
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