Steps in the Pathogenesis of Multiple Sclerosis - I: From Neuroinflammation to Neurodegeneration

Abstract

Inflammation has been described as a deleterious factor in MS immunopathogenesis for a long time. However, recent studies have proved the neuronal protective and efficacious effects of inflammation. Inflammation in the brain is a double-edged process that may be beneficial in promoting homeostasis and repair, but can also result in tissue injury through the damaging potential of inflammatory mediators. Control mechanisms that minimize the extent of the inflammatory reaction are necessary in order to preserve brain architecture and restore function. The end result of the inflammatory process, neurotoxicity and/or neuroprotection, is a function of the fine balance between the two cellular systems and of the complex signaling relationships between anti-inflammatory neuroprotective factors. In central nervous system inflammation the extent of tissue injury depends on both native and adaptive elements of the immune system. Besides, inflammation is not limited with the invasion of exogeneus cells infiltrating from the blood brain barrier. Astrocytes and microglial cells as being endogeneous also play an important role in the process. Secondary inflammatory mediators from these cells trigger the unique local inflammation of central nervous system. In the active MS plaques distinct cytokines and chemokines have been determined. Conclusion: Inflammation has different aspects and some proof of beneficial roles can be summarized: Before the clinical signs of /during the experimental allergic encephalomyelitis (EAE) the presence of IFN-gamma has been shown as a limitting factor for the progression, the delivery of antiIFN-g monoclonal antibodies have increased the morbidity in EAE. CD4+ T cells stimulate microglial cells to secrete some mediators as interleukin E2 that can supress IL-12 and the same cells can also secrete neruprotective factors as brain derived neurotrophic factor. Another group of cells, macrophages trigger remyelinization by clearing myelin debris. This review discusses about the contradictory effects of inflammation on the immunopathogenesis of multiple sclerosis. It outlines the cells responsible for the inflammatory cascade, both beneficial and detrimental effects of inflammation on myelin and axonal integrity and additional relation for demyelination and axonal transsection.