Systemic interferon therapy of multiple sclerosis: the pros.

The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is generally believed to be due to an immunologic response in a genetically predisposed individual, localized within the CNS white matter, and triggered by exposure to an environmental agent such as a virus. In a randomized, double-blind, placebo-controlled, crossover trial of systemic natural alpha IFN in 24 patients with exacerbating-remitting MS, patients with a strictly exacerbating-remitting course showed a reduction in the frequency and severity of exacerbations, while those with exacerbations superimposed upon a chronic progressive course did not benefit from this treatment, primarily because of side effects that included fever, malaise, and fatigue. Since the performance of this study, it has been shown that the preparation of natural human alpha interferon used in this trial may lead to side effects in some individuals through the production of immune complexes (ICs). These ICs were due to the generation of antibodies reacting with residual Sendai virus proteins used in the preparation of the IFN, and retained in the final formulation. The encouraging results of this and other preliminary studies of alpha or beta IFN but not gamma IFN therapy in MS, coupled with the current availability of more highly purified interferon preparations, warrants further clinical trials of IFN in MS, focusing on beta interferon preparations in particular.