In the Brown Norway (BN) rat,
mercuric chloride (HgCl(2)) induces a T(h)2-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 HgCl(2)-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 HgCl(2) + saline, HgCl(2) +
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 HgCl(2)-enhanced
IgE expression on mast cells with a trend to a decrease in HgCl(2)-enhanced
IL-4 expression in these cells. In addition, there was an increased rat mast cell
protease (
RMCP) II concentration in the serum after HgCl(2) injection and the elevated levels of
RMCP II stimulated by HgCl(2) were totally abolished by the administration NAC in the HgCl(2) + NAC group. However, there was no significant change in serum total
IgE concentrations between the HgCl(2) + saline group and the HgCl(2) + NAC group. The non-sulphydryl-containing
antioxidants desferrioxamine and
pyruvate demonstrated a similar effect in inhibiting HgCl(2)-induced early
vasculitis. Our data show that administration of an
antioxidant to BN rats reduces HgCl(2)-induced early
vasculitis, suggesting that oxidative stress plays a role in the pathogenesis of HgCl(2)-induced early
vasculitis. This finding may have implications for the understanding of the initiation in this experimental model of T(h)2 cell-driven autoimmunity and possibly of analogous human diseases.