Therapeutic role of beta-interferons in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). In the last 12 years, there has been a proliferation of studies elucidating the immune mechanisms that mediate tissue damage in MS. Interferons (IFNs) have an important role in regulating innate and adaptive immune responses. They decrease pro-inflammatory responses such as the autoimmunity in MS, but other autoimmune responses such as systemic lupus erythematosus (SLE) may be exacerbated. This review offers a general overview of the biological properties of IFNs, effects on immune cells, and clinical effectiveness in MS treatment. IFN signaling is complex, from receptor binding events to the generation of effector mechanisms that dampen inflammation. Immune cell function is altered in MS. IFN treatment of MS patients ameliorates immune dysfunction, but not completely. The incomplete resolution of immune dysfunction by IFNs partly explains their significant, but modest therapeutic effects. This observation also suggests that there are immune mechanisms in MS that are resistant to IFN therapy. In MS, abnormalities may exist at several points along the IFN signaling pathway, including molecular defects in the IFN second messenger system. Currently, several studies are ongoing evaluating ways of potentiating IFN effects. IFNs were the first agents to show clinical efficacy in treatment of MS. More than a decade of experience with IFNs has showed continued clinical efficacy over time. In the near future, IFNs will continue to play a major role in MS.