Desferrioxamine modulates chemically induced T helper 2-mediated autoimmunity in the rat.
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.
Wu
Z
Z
Department of Cellular and Molecular Medicine, St George's Hospital Medical School, London, UK. z.wu@sghms.ac.uk
Holwill
S D J
SD
Oliveira
D B G
DB
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D003676:Deferoxamine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D008627:Mercuric Chloride / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology
D007502:Iron Chelating Agents; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma; D003676:Deferoxamine