Autoimmunity / iron chelator / oxidative stress



Clin Exp Immunol. 2004 Feb; 135(2): 194-9. Related Articles, Links

Desferrioxamine modulates chemically induced T helper 2-mediated autoimmunity in the rat.

Wu Z, Holwill SD, Oliveira DB.

Department of Cellular and Molecular Medicine, St George's Hospital Medical School, London, UK.

A rise in interleukin (IL) 4-dependent immunoglobulin E (IgE) is a hallmark of the mercuric chloride
(HgCl2)-induced Th2-mediated autoimmune syndrome in the Brown Norway (BN) rat, and one of the
mediators in allergic asthma in human. Oxidative stress, a potential factor related to the
pathogenesis of allergy and asthma, has been shown to up-regulate IL-4 in mast cells and predispose
to degranulation in vitro. However, it remains unknown whether oxidative/antioxidative imbalance
plays a role in this Th2-driven model of autoimmunity in the rat. Here we show that administration
of the non-sulphydryl-containing antioxidant desferrioxamine i.p. and s.c. to BN rats reduces HgCl2-
enhanced IL-4 gene expression and inhibits HgCl2-induced Th2-mediated autoimmunity. Desferrioxamine
treatment suppresses significantly IgE production and lymphoproliferation, and reduces tissue injury
in the form of caecal vasculitis in the HgCl2-induced autoimmune syndrome. These results support a
role for oxidative stress in the pathogenesis of the HgCl2-induced Th2-dominated autoimmune
syndrome. This finding might have implications for understanding the mechanisms involved in Th2 cell
responses as seen in allergy and asthma and thereby aid the development of new therapeutic
strategies for these diseases.

PMID: 14738445 [PubMed - in process]


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