Cytokines as Novel Therapeutic Agents for Neuroinflammatory Disorders: A Role for Interferon-β in the Treatment of Multiple Sclerosis

Moiz      Bakhiet

Abstract

Cytokines are proteins that play an important role in the control of different diseases but, produced in excess or in the wrong site, they can cause pathological changes. The existence of the basic effector subsets of proinflammatory and anti-inflammatory cytokines is now well accepted, and is being used to plan therapeutic strategies for inflammatory and autoimmune disorders. Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). It is considered as an autoimmune disease associated with immune activity directed against CNS antigens. Immune mechanisms involving proinflammatory cytokines are believed to play an important role in the pathogenesis of MS. Thus, immunosuppression and immunomodualtion have become a focus of therapeutic strategies in MS. Recombinant interferon-beta (IFN-β) has been introduced as a drug and was considered to be the first breakthrough in the treatment of multiple sclerosis. Placebo-controlled, double-blind studies, have demonstrated the efficacy of three different forms of IFN-β administrated by either subcutaneous or intramuscular routes and at different doses in patients with active relapsing-remitting MS (RR-MS). These drugs are IFN-β-1b (Betaferon®) and IFN-β-1a (Avonex® and Rebif®). Different clinical trials demonstrated clear benefits of IFN-β for decreasing relapses and probability of sustained clinical disability progression in patients with RR-MS as assessed by brain magnetic resonance imaging (MRI). Beneficial effects in secondary progressive MS (SP-MS) was also reported. This review addresses the introduction of cytokines as novel and effective therapeutic agents as demonstrated by IFN-β in the treatment for MS. Further evaluation for combination of therapeutic immunomodulatory agents should be considered.