INTERFERON-BETA DECREASES T-CELL ACTIVATION AND INTERFERON-GAMMA PRODUCTION IN MULTIPLE-SCLEROSIS

Interferons (IFN) are biological molecules with anti-viral, anti-proli ferative and immunomodulatory actions. There is evidence that IFN-gamm a increases the frequency of exacerbations of multiple sclerosis (MS) whereas IFN-beta may reduce their frequency. Here we present evidence that IFN-beta significantly decreases concanavalin A (Con A)-induced p roliferation of peripheral blood mononuclear cells (PBMC) of MS patien ts and healthy individuals. Similar results were obtained when PBMC we re activated through the T cell receptor (TcR) by anti-CD3 monoclonal antibody or independently of it by phorbol ester and Ca2+ ionophore. T hese effects of IFN-beta were also noted when IFN-gamma and IFN-beta w ere added together. Furthermore, IFN-beta decreased proliferation when added to cells that were already pre-activated. Activated CD4+ and CD 8+ T cells were downregulated to approximately the same extent. Analys is of cytokine production showed that IFN-gamma production by Con A ac tivated PBMC was increased in MS when compared to controls. IFN-beta s ignificantly decreased IFN-gamma production in MS patients and control individuals. Con A activated cultures treated with IFN-beta showed de creased IL2R expression and accumulation of IL2. These results show th at IFN-beta decreases T cell activation and IFN-gamma production in vi tro, effects that may be beneficial in MS.