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

Ann Neurol. 1995 Jan;37(1):82-8. doi: 10.1002/ana.410370115.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-10 / genetics
  • Leukocytes, Mononuclear / physiology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / physiopathology
  • Polymerase Chain Reaction
  • Prospective Studies
  • RNA, Messenger / analysis*
  • Recurrence
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism


  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10