The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine...

Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p<0.007-0.03), while the IL-6 production increased (p<0.03). No significant change was observed in the MBP-induced CD4+ T cell proliferation, or in the production of IL-4, IL-5 and brain-derived neurotrophic factor. In comparison, IFN-beta therapy reduced IFN-gamma and IL-4 responses to TT (p<0.003 and p<0.04). Thus, IFN-beta inhibits IFN-gamma production in general, presumably alleviating the detrimental influence of IFN-gamma in MS. However, the increase in proinflammatory IL-6 and the decrease in anti-inflammatory IL-10 responses suggest that IFN-beta has more diverse effects than previously assumed.