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Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is
P Rieckmann1, M Albrecht, B Kitze
1Department of Neurology, University of Göttingen, Germany.
Abstract:
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.
Insights
Cytokine messenger RNA (mRNA) levels, particularly tumor necrosis factor-alpha mRNA, increase before relapses in relapsing-remitting multiple sclerosis patients. This finding may help monitor disease activity.
Area of Science:
- Immunology
- Neuroscience
- Molecular Biology
Background:
- Relapsing-remitting multiple sclerosis (RRMS) is characterized by unpredictable disease activity.
- Monitoring immunological status in RRMS is crucial for effective management and clinical trials.
Purpose of the Study:
- To investigate the correlation between cytokine messenger RNA (mRNA) expression patterns in blood mononuclear cells and disease activity in RRMS patients.
- To identify potential biomarkers for predicting or monitoring MS relapses.
Main Methods:
- Longitudinal study of 29 RRMS patients over 12 months, with blood mononuclear cell sampling every 4 weeks.
- Semiquantitative polymerase chain reaction (PCR) to measure cytokine mRNA expression (TNF-α, LTa, TGF-β, IL-10, IL-1β, IL-4, IL-6, IFN-γ).
- Assessment of disease activity through clinical relapse evaluation and magnetic resonance imaging (MRI) for new lesions.
Main Results:
- Significant increases in tumor necrosis factor-alpha (TNF-α) and lymphotoxin-alpha (LTα) mRNA expression preceded clinical relapses by approximately 4 weeks in 85% of cases.
- Transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) mRNA levels decreased prior to relapses.
- Fluctuations in TNF-α mRNA were also observed in patients with stable disease but active MRI scans.
- No significant correlation was found between disease activity and mRNA expression of IL-1β, IL-4, IL-6, interferon-gamma, or endothelin-1.
Conclusions:
- Cytokine mRNA expression patterns in peripheral blood mononuclear cells correlate with disease activity in RRMS.
- Elevated TNF-α and LTα mRNA expression may serve as early indicators of impending relapses.
- Monitoring cytokine mRNA profiles could be a valuable tool for assessing immunological status in RRMS patients during clinical trials.