Immune-mediated demyelination.
The Guillain-Barré syndrome (GBS) and multiple sclerosis (MS) are thought to result from aberrant immune responses to myelin antigens. Recent evidence to implicate the cytokine tumor necrosis factor-alpha (TNF-alpha) and the intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of these disorders is reviewed. In GBS, elevated serum concentrations of TNF-alpha are detectable in 20 to 50% of patients. TNF-alpha released from autoreactive T cells, macrophages, or microglia may contribute to inflammatory demyelinative processes by upregulating the expression of recognition molecules on antigen-presenting cells; by cytotoxic damage to endothelium; by stimulating the secretion of inflammatory mediators; by directly injuring the myelin sheath; or by interfering with impulse propagation. Its pathogenic potential in GBS is underscored by findings in experimental autoimmune neuritis. Soluble ICAM-1, originating from T cells, macrophages, endothelium, or glial cells, circulates at increased concentrations in serum and cerebrospinal fluid of patients with active MS. ICAM-1 may be crucially involved in the migration of autoreactive T lymphocytes from blood to brain. Whether ICAM-1 can serve as a marker of acute inflammatory events in MS associated with clinical relapses warrants further investigation. TNF-alpha and ICAM-1 could be targets for antigen nonspecific treatment approaches to the inflammatory demyelinating diseases GBS and MS.
Hartung
H P
HP
Clinical Research Group for Multiple Sclerosis, Julius-Maximilians-Universität Würzburg, Germany.
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002448:Cell Adhesion; D003711:Demyelinating Diseases / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D011129:Polyradiculoneuropathy / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015703:Antigens, CD; D014409:Tumor Necrosis Factor-alpha