International Immunology, Vol. 14, No. 3, 267-273,
March 2002
© 2002 Japanese Society for Immunology
Antioxidants inhibit mercuric chloride-induced early vasculitis
Divisions of Renal Medicine and
1 Histopathology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
Correspondence to: Z. Wu; E-mail: z.wu{at}sghms.ac.uk
In the Brown Norway (BN) rat, mercuric chloride (HgCl2) induces a Th2-dominated autoimmune syndrome which includes an early phase of mast cell-dependent vasculitis. We have shown in vitro that oxidative stress up-regulates IL-4 in mast cells and predisposes to degranulation. The aim of this study was to determine whether administration of antioxidants inhibits HgCl2-induced early vasculitis in vivo, and, if so, to examine whether modulation of the oxidative/antioxidative balance influences IgE and IL-4 expression by mast cells in situ. Groups of rats were given HgCl2 + saline, HgCl2 + N-acetyl-L-cysteine (NAC), saline + saline or saline + NAC respectively and blood was taken and animals killed 48 h later. NAC significantly reduced both HgCl2-induced early vasculitis and HgCl2-enhanced IgE expression on mast cells with a trend to a decrease in HgCl2-enhanced IL-4 expression in these cells. In addition, there was an increased rat mast cell protease (RMCP) II concentration in the serum after HgCl2 injection and the elevated levels of RMCP II stimulated by HgCl2 were totally abolished by the administration NAC in the HgCl2 + NAC group. However, there was no significant change in serum total IgE concentrations between the HgCl2 + saline group and the HgCl2 + NAC group. The non-sulphydryl-containing antioxidants desferrioxamine and pyruvate demonstrated a similar effect in inhibiting HgCl2-induced early vasculitis. Our data show that administration of an antioxidant to BN rats reduces HgCl2-induced early vasculitis, suggesting that oxidative stress plays a role in the pathogenesis of HgCl2-induced early vasculitis. This finding may have implications for the understanding of the initiation in this experimental model of Th2 cell-driven autoimmunity and possibly of analogous human diseases.
Keywords: antibodies and autoimmunity, cytokines, in vivo animal model, mast cells