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 > or = 4.0 and > or = 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 proinflammatory mediator, is associated with MS-related fatigue. This is in support of a pathogenic role of the MS-related inflammatory process in the development of fatigue.
Flachenecker
Peter
P
Department of Neurology, Julius-Maximilians University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany. peter.flachenecker@surfeu.de
Bihler
Irene
I
Weber
F
F
Gottschalk
M
M
Toyka
Klaus V
KV
Rieckmann
Peter
P
D000328:Adult; D005221:Fatigue / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000235:genetics* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma