T-cell interferon-γ, tumor necrosis factor-α and interleukin-6 receptor binding in patients with multiple sclerosis.: Effects of interferon-β 1b treatment

Introduction. Multiple sclerosis (MS) is a T-cell-mediated demyelinating disease of the central nervous system (CNS), in which the cytokine network may be deranged. Interferon (IFN)-gamma interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are cytokines with several effects on the neuroimmune system. Specific IFN-gamma, IL-6, and TNF-alpha receptors have been found on human lymphocytes and other cell types. Patients and methods. We assayed IFN-gamma, TNF-alpha, and IL-6 binding on peripheral blood T cells from MS patients, as compared with healthy subjects. T cells from MS patients have significantly less IFN-gamma receptors, and more TNF-alpha and IL-6 receptors than those from controls. Such receptors are of the same type in patients and healthy subjects. By comparing MS patients' subgroups with each other, significant differences in mean B-max values have been found between patients in a stable phase and those in relapse, and between stable patients and those in an evolutive phase. As far as IL-6 binding is concerned, significant differences in mean B-max values were observed only between patients in stable phase and those in relapse. Results. T lymphocytes from untreated MS patients, which had significantly smaller amounts of IFN-gamma receptors than those from controls, and more TNF-alpha and IL-6 receptors than controls showed a significant increase in IFN-gamma binding, and a significant decrease in TNF-alpha and IL-6 binding after a 3-month IFN-beta(1b) treatment. T-cell IFN-gamma B-max values were even higher and those of TNF-alpha and IL-6 were lower after 6 months. Conclusion. We discuss these results in terms of MS immunopathophysiology, since activated T cells have decreased IFN-gamma, and increased TNF-alpha and IL-6 receptor amounts.