Heat Shock Proteins and Multiple Sclerosis

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) with myelin damage (loss of myelin sheaths and eventually secondary axon damage). In most of cases it evolves from a relapsing-remitting phase to a chronic progressive one which brings about stable disability and handicap. In spite of the scanty certainties about its etiology, the pathogenesis of MS is widely accepted to be autoimmune based on: 1. A potentially disregulated immune response in patients compared to controls (the presence of immunocompetent cells not only inside the MS lesions but also as autoreactive, “in-vivo”-activated effectors in the peripheral blood or in the cerebrospinal fluid of patients; the presence of immuno-globulin oligoclonal bands in the cerebrospinal fluid of patients; the association with “at risk” MHC haplotypes in patients). 2. The pathogenetic role of such autoreactive effectors in studies on the animal model of MS, experimental allergic encephalomyelitis (EAE); in rodents and in primates, the encephalitogenicity of myelin-specific T lymphocytes (alone or in combination with myelin-specific antibodies) has been demonstrated. 3. Finally, and most importantly, the therapeutic efficacy of strategies aimed at deleting or antagonizing the pathogenic autoaggressive effectors; most of the treatments, recently implemented in MS with encouraging results, tend to modulate, more or less specifically, the disregulated immune response of the patients. Examples of such therapies include interferon s, copolymer-1 and intravenous high-dose immunoglobulins.