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

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.