Clinical trials of interferons in multiple sclerosis. What have we learned?

Although multiple sclerosis (MS) is generally believed to be an immune-mediated disease, conventional therapy with ACTH, corticosteroids, or immunosuppressive drugs is unsatisfactory. Aside from their unpredictable therapeutic effects, these agents are potentially hazardous and can only be given for short periods of time. There is an urgent need for less toxic yet effective immunotherapy, that that can be administered early in the disease and continued indefinitely. Clinical trials of the interferons (IFNs) have not only led to a promising new approach to treatment, but have also stimulated basic research in the immunological mechanisms of underlying disease activity. Administration of IFN-gamma promotes exacerbations of MS, whereas recombinant IFN-beta has been shown, in controlled clinical trials, to suppress them. Other ongoing studies are likely to provide further information about its long-term therapeutic value. More importantly, laboratory studies performed in conjunction with these clinical trials have provided fresh insights into the pathogenesis of MS by revealing immunoregulatory mechanisms in which endogenous IFN-gamma, TNF-alpha, and other cytokines appear to play central roles. The 'Decade of the Brain' may therefore see answers both to the therapeutic dilemma of MS, and to more basic questions about the function of IFNs and other cytokines in activation and regulation of the disease process.