Termination of inflammation in the nervous system.
T cell apoptosis has been studied in animal models for human autoimmune disorders of the nervous system and in other tissues devoid of specialized immune-defense mechanisms. Our data suggest that the central nervous system has a high potential to eliminate T cell inflammation, whereas this mechanism is less effective in the peripheral nervous system, and even more in muscle and skin. In-vitro experiments indicate different scenarios how specific cellular and humoral elements in the nervous system may synergize and sensitize T cells for apoptosis in-vivo. Probably release of TNF-alpha in the nervous system is a central mechanism to limit inflammation in the brain. This is further substantiated since neutralization of TNF-alpha in MS patients increased cellular inflammation and relapses. Therapeutically several conventional and novel approaches like glucocorticosteroids and high-dose antigen therapy induce T cell apoptosis in-situ. We also discuss regulatory, proapoptotic mechanisms such as the Fas/FasL system and counterregulatory mechanisms that have been utilized to limit tissue damage.
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Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. ralph.gold@rub.de
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D017628:Microglia / Q000502:physiology; D009420:Nervous System / Q000276:immunology* / Q000473:pathology; D013256:Steroids / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000893:Anti-Inflammatory Agents; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha