Reactive oxygen species in the initiation of IL-4 driven autoimmunity as a potential therapeutic target.
Helper T-lymphocytes have been shown to differentiate into two mutually regulatory subsets. Cells primarily secreting interleukin-2 (IL-2) and interferon-gamma are known as Th1 cells and mediate classical cell-mediated immune responses such as delayed-type hypersensitivity. Cells secreting interleukin-4 (IL-4) are known as Th2 cells and promote humoral immune responses, in particular the production of IgE and IgG4 (human) or IgG1 (rodents). Over-activity of either cell type can result in tissue-damaging autoimmune disease. A number of human diseases including asthma and some kidney diseases are thought to be caused by a Th-2 type autoimmune response. Study of an animal model of Th2-driven autoimmunity (mercuric chloride-induced autoimmunity in Brown Norway rats) has yielded insights into a possible role for oxidant stress in the generation of Th-2 driven autoimmune responses. Mercuric chloride probably causes oxidant stress by the generation of free-radicals, activating NK-kappaB, a transcription factor for the IL-4 gene. Treatment with the antioxidants N-acetlcysteine and desferrioxamine has been shown to suppress vasculitis and IgE production in this model. These findings suggest a possible clinical role for antioxidants in the therapy of human autoimmune disease.
Wu
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Department of Cellular and Molecular Medicine-Renal Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. zwu@sghms.ac.uk
MacPhee
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D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic
D000276:Adjuvants, Immunologic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D015847:Interleukin-4