Cytokine mRNA expression in patients with multiple sclerosis and fatigue

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). Cytokine mRNA expression for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were measured by real time RT PCR. Autonomic 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-alpha mRNA expression were significantly higher in MS patients with (FSS greater than or equal to 4.0 and greater than or equal to 5.0, n = 26 and n = 14, respectively) than in those without fatigue (FSS < 4.0, n = 11). No differences were seen for IFN-gamma and IL-10 mRNA expression. Cytokine levels were not correlated to autonomic tests or to serum catecholamine levels. Conclusions: These results suggest that TNF-alpha, as a principal pro inflammatory mediator, is associated with MS-related fatigue. This is in support of a pathogenic role of the MS-related inflammatory pro cess in the development of fatigue.