Interferons (IFNs) are small molecules (cytokines) produced by cells of the immune system in response to a variety of inducers, especially viruses. They have been demonstrated to have antiviral, antiproliferative, and immunomodulating properties and are divided into two types: type 1 includes alpha and beta IFN; type 2 is gamma IFN. Interferons were initially considered for the treatment of MS because of a presumed viral pathogenesis. There was some evidence for a decrease in the level of IFN gamma in the CSF of MS patients, and a pilot study was performed to assess the safety and efficacy of IFNs. This trial was prematurely terminated because of an unexpected increase in the relapse rate. The negative result of this trial provided an important clue to the understanding of the pathogenesis of MS, and subsequent studies focused on the effects of type 1 IFNs because they were found to have a number of immunomodulatory effects that were quite the opposite of those of IFN gamma. IFN alpha and beta use the same receptor and have similar effects and a high degree of homology.

Initially, a number of studies reported limited efficacy for intrathecally, subcutaneously, and intramuscularly administered type 1 IFN in decreasing the frequency of exacerbations in relapsing-remitting MS (RRMS). In several of these studies, these effects were shown to be reversible, with the return of markers of disease activity to baseline after discontinuation of treatment. This supported the hypothesis that the observed changes were indeed the result of IFN therapy. Therefore, further studies were performed, which took advantage of the availability of recombinant IFN and abandoned natural IFN. At present, two forms of recombinant IFN beta (1a [Avonex®and Rebif®] and 1b [Betaseron®/Betaferon®]) have been approved by regulatory authorities. Each is made by recombinant DNA technology in tissue culture and are highly purified before use. IFN beta-1a is a glycosylated, recombinant mammalian-cell product, with an amino acid sequence identical to that of natural interferon beta. IFN beta-1b is a nonglycosylated recombinant bacterial-cell product in which serine is substituted for cysteine at position 17.