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Rationale for immunotherapy in multiple sclerosis
1Department of Neurology, University of Alabama at Birmingham 35294-0007.
The presumed but unspecified immune-mediated basis for the pathogenesis of multiple sclerosis (MS) has led to therapeutic attempts to modify the immune system in general and in selective ways in patients with MS. In general, antiviral, anti-inflammatory, immunosuppressant, and immunomodulatory therapies have been considered. More specifically, these treatments have involved the use of glucocorticoids; immunosuppressant drugs and physical agents such as irradiation; modifications of the immune environment with therapeutic plasma exchange and intravenous immunoglobulin; and more recently, alteration of events surrounding antigen presentation and stages of the immune response of cellular proliferation, recruitment, and infiltration of the central nervous system. The more selective approaches have dealt with attempts to interfere with elements of the trimolecular complex through blocking MHC class II, modifying T-cell receptor functions, interfering with co-stimulatory recognition steps, and altering cytokine effects or lymphocyte adhesion. The rationale for the current therapeutic trials of antigen-driven peripheral tolerance, MHC class II blockade, and immunomodulation, especially with interferon-beta, illustrate the progression from broad immunosuppressive treatment to targeting specific activities of the immune system. The combination of new strategies in immunotherapy and sensitive disease monitoring of their effects should allow for more rapid identification of beneficial and tolerated treatment for MS.
The presumed but unspecified immune-mediated basis for the pathogenesis of multiple sclerosis (MS) has led to therapeutic attempts to modify the immune system in general and in selective ways in patients with MS. In general, antiviral, anti-inflammatory, immunosuppressant, and immunomodulatory therapies have been considered. More specifically, these treatments have involved the use of glucocorticoids; immunosuppressant drugs and physical agents such as irradiation; modifications of the immune environment with therapeutic plasma exchange and intravenous immunoglobulin; and more recently, alteration of events surrounding antigen presentation and stages of the immune response of cellular proliferation, recruitment, and infiltration of the central nervous system. The more selective approaches have dealt with attempts to interfere with elements of the trimolecular complex through blocking MHC class II, modifying T-cell receptor functions, interfering with co-stimulatory recognition steps, and altering cytokine effects or lymphocyte adhesion. The rationale for the current therapeutic trials of antigen-driven peripheral tolerance, MHC class II blockade, and immunomodulation, especially with interferon-beta, illustrate the progression from broad immunosuppressive treatment to targeting specific activities of the immune system. The combination of new strategies in immunotherapy and sensitive disease monitoring of their effects should allow for more rapid identification of beneficial and tolerated treatment for MS.