TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA EXPRESSION IN PATIENTS WITHRELAPSING-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 multip le sclerosis every 4 weeks over a period of 12 months. During this per iod 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 reactio n we demonstrated significant increases in tumor necrosis factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a rela pse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA expression preceded clinical symptoms by 4 weeks. A similar patte rn was observed for lymphotoxin mRNA expression. At the same time, tra nsforming growth factor-beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor-alpha wer e also observed in 6 patients with Stable disease who had active magne tic resonance scans on follow-up. No correlation of disease activity w as observed with interleukin-1 beta, -4, or -6, inferferon gamma or en dothelin-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 scler osis. It may be a valuable parameter to monitor the immunological stat us of patients in future clinical trials.