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Current Pharmaceutical Design

Eiditor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Reactive Oxygen Species in the Initiation of IL-4 Driven Autoimmunity as a Potential Therapeutic Target

Author(s): Z. Wu, I. A. M. MacPhee and D. B. G. Oliveira

Volume 10 , Issue 8 , 2004

Page: [899 - 913] Pages: 15

DOI: 10.2174/1381612043452875

Price: $58

Abstract

Helper T-lymphocytes have been shown to differentiate into two mutually regulatory subsets. Cells primarily secreting interleukin-2 (IL-2) and interferon-g 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-kB, 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.

Keywords: autoimmunity, antioxidants, th2, mercuric chloride


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