Tumor necrosis factor‐α messenger RNA expression in patients with relapsing‐remitting multiple sclerosis is associated with disease activity

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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‐α mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor‐α mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor‐β and interleukin‐10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor‐αwere 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‐1β, ‐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.