Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity.
We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing-remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2-weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor-beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor-alpha were also observed in 6 patients with stable disease who had active magnetic resonance scans on follow-up. No correlation of disease activity was observed with interleukin-1 beta, -4, or -6, inferferon gamma or endothelin-1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing-remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.
Rieckmann
P
P
Department of Neurology, University of Göttingen, Germany.
Albrecht
M
M
Kitze
B
B
Weber
T
T
Tumani
H
H
Broocks
A
A
Lüer
W
W
Helwig
A
A
Poser
S
S
D000328:Adult; D001483:Base Sequence; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis*; D012008:Recurrence; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10