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  • Title: Low-dose mercuric chloride induces resistance in brown norway rats to further mercuric chloride by up-regulation of interferon-gamma.
    Author: Szeto C, Gillespie KM, Mathieson PW.
    Journal: Scand J Immunol; 1999 Aug; 50(2):195-201. PubMed ID: 10447925.
    Abstract:
    Mercuric chloride induces autoimmunity in Brown Norway rats with polyclonal B-cell activation, hyper-IgE and multiple autoantibodies. Pre-treatment with low-dose HgCl2 (one-tenth of the standard dose) induces resistance to later full-dose HgCl2; we have studied the mechanism of this resistance. Brown Norway rats given low-dose HgCl2 showed only a modest increase in serum IgE level, three logs lower than rats given standard-dose HgCl2, and no up-regulation of splenic interleukin (IL)-4 mRNA. There was up-regulation of splenic interferon (IFN)-gamma gene expression and a progressive rise in serum IFN-gamma. Neither IL-12 nor IL-18 were induced, but there was up-regulation of IL-12 receptor beta2-chain (IL-12Rbeta2) expression. IL-10 and transforming growth factor (TGF)-beta expression did not change. Serum IgE and splenic IL-4 mRNA expression remained static when these rats were rechallenged, confirming resistance. Thereafter IFN-gamma expression gradually fell, after which IL-4 expression and serum IgE rose slightly. Our observations suggest that low-dose HgCl2 confers protection in Brown Norway rats to further HgCl2 by up-regulation of IFN-gamma, associated with enhanced IL-12Rbeta2 expression. The immunological response to HgCl2 in susceptible rat strains is more complex than previously appreciated and is dose dependent, with low doses inducing a T helper '(Th)1' type of response in contrast to the 'Th2' type response associated with standard doses.
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