Interferon beta 1a

Historical note and nomenclature
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By K K Jain MD

 Interferons are glycoproteins secreted in the body in response to viral infections and are presumed to provide protection to other cells against viral infection. The name derives from the term "viral interference" used in the first description of these proteins by their discoverers (Isaacs and Lindemann 1957). In addition to the antiviral properties, immunomodulatory and antineoplastic properties of interferons were discovered later (Borden and Ball 1981). Use of interferons in multiple sclerosis was based on the belief that the disease may be due to a latent virus infection of the brain in persons with impairment of the immune system (Cook and Dowling 1980). Trials with interferon have been conducted in various diseases of the nervous system including multiple sclerosis (Fleishman et al 1988). Two types of interferons have been identified: type 1 (interferon alpha and interferon beta) and type 2 (interferon gamma). Type 2 is synthesized mainly by lymphocytes and type 1 beta by fibroblasts, but both have a similar amino acid composition and genetic coding. Gamma interferon differs from type 1 interferons by its amino acid composition and cell surface receptor. Interferon alpha has been developed mostly for applications in virology and oncology. Interferon beta has a beneficial effect on the course of multiple sclerosis, and interferon alpha has an equivocal effect, whereas interferon gamma exacerbated the disease. Reasons for these various effects are not well understood. History of development of interferon beta therapy for multiple sclerosis has been reviewed elsewhere (Stock and Horowski 2001). Descriptions in this article are based on interferon beta 1a and a separate article is devoted to interferon beta 1b.

Interferons are now manufactured commercially in large quantities by recombinant DNA technology. United States Food and Drug Administration approved interferon beta 1a for intramuscular injection in 1996 (Avonex by intramuscular injection). Another preparation of interferon beta 1a for subcutaneous injection was approved in the United States in 2002 (Rebif by subcutaneous injection).

The amino acid sequence of Avonex (R) is identical to that of natural human interferon beta. It cannot be compared with other interferon betas because of the differences in reference standards. Moreover, the route of administration affects the action, and intramuscular preparation is distinct from the subcutaneous injection preparation, interferon beta 1a (Rebif), which was approved in the United States in 2002. Both preparations have been compared in clinical trials.