Relapse markers in multiple sclerosis: are in vitro cytokine production changes reflected by circulatory T-cell phenotype alterations?

In vitro tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production, serum neopterin levels, and T-lymphocyte subpopulations were determined on a monthly basis in 22 MS patients. 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. These increases were not reflected by changes in T-lymphocyte subpopulations. However, significant differences in T-cell subsets were observed between controls and relapsing progressive patients.