Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations?

Acta Neurol Scand. 1988 Oct;78(4):318-23. doi: 10.1111/j.1600-0404.1988.tb03663.x.


We have carried out a longitudinal study of interferon (IFN) and tumor necrosis factor (TNF) using a whole-blood mitogen stimulation assay in 20 multiple sclerosis (MS) patients and in a healthy control group. We set up individual profiles and the results were quite constant for each individual, both in healthy donors and in the patients in remission. Before exacerbations, however, we found an increase of IFN-gamma and TNF production preceding clinical symptoms by a maximum of 2 weeks. In benign cases, the increase disappeared rapidly, even before the appearance of symptoms, whereas we found sequelae whenever the increase persisted during weeks. In chronic progressive patients, we frequently found intervening increases. It may be that IFN-gamma and TNF trigger off exacerbations at a very early stage and that these cytokines may also play a role in maintaining disease in chronic progressive and invalidating forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / adverse effects
  • Interferon-gamma / biosynthesis*
  • Leukocytes / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / metabolism*
  • Predictive Value of Tests
  • Recurrence
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Tumor Necrosis Factor-alpha
  • Interferon-gamma