Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease.

T HE ETIOLOGY AND pathogenesis of multiple sclerosis (MS) have been much debated during the past 50 years. It is now recognized that MS is a complex disease with different clinical and pathological phenotypes, perhaps reflecting different pathways to tissue injury. Thus, MS may not be a single disease entity. Nonetheless, with recent advances in immunology and magnetic resonance imaging and the demonstration that immunomodulatory treatment can have an ameliorating effect on the disease process, it is now clear that the core process in MS is inflammatory, with T cells and their mediators triggering injury of axons and their myelin sheaths through a complex sequence of events. The Tcell–mediated inflammation is driven by an autoimmune process, which in turn can trigger a degenerative phase that is immune independent. As described below, a large body of evidence suggests there is a Th1-type bias in MS (interferon [IFN] gamma, interleukin [IL]12, IL-18, and osteopontin) and that factors associated with Th2-type (IL-4 and IL-10) or Th3-type (transforming growth factor ) responses are beneficial in MS. Immune abnormalities in MS include activated T cells in the blood and cerebrospinal fluid, T-cell reactivity to myelin antigens, Th1-type inflammation in the brain (IL-12 and chemokine expression), local central nervous system (CNS) immune reaction (Ig-G), linkage of immune abnormalities to clinical course and magnetic resonance imaging, and major histocompatibility complex linkage.