In vitro TNF-alpha, IL-2 and IFN-gamma production as markers of relapses in multiple sclerosis.

In 22 patients with definite multiple sclerosis (MS) we determined with monthly intervals over a period of 24 months the in vitro tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-2 (IL-2) production and the serum neopterin levels. The results were compared with normative data collected from 14 healthy controls over the same period. Twenty-nine relapses in 13 patients were noticed. We found increased in vitro TNF-alpha production from 4 weeks on prior to the day of an exacerbation. There was a significant correlation with in vitro IFN-gamma release, the absolute blood monocyte count and the serum neopterin levels, suggesting that monocytes stimulated by IFN-gamma play an important role in the TNF-alpha production. Serial analysis of in vitro TNF-alpha production proved to be a helpful tool in predicting relapses in MS patients. Furthermore, elevated levels of IFN-gamma and IL-2 after stimulation with OKT3 during exacerbations were demonstrated. Serial analysis of these two biological markers revealed to be of no value in predicting relapses.