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Low‐Dose Mercuric Chloride Induces Resistance in Brown Norway Rats to Further Mercuric Chloride by Up‐Regulation of Interferon‐γ
Author(s) -
CheukChun Szeto,
K. M. Gillespie,
Peter W. Mathieson
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00584.x
Subject(s) - immunoglobulin e , medicine , endocrinology , interleukin 4 , gene expression , chemistry , biology , cytokine , immunology , gene , antibody , biochemistry
Mercuric chloride induces autoimmunity in Brown Norway rats with polyclonal B‐cell activation, hyper‐IgE and multiple autoantibodies. Pre‐treatment with low‐dose HgCl 2 (one‐tenth of the standard dose) induces resistance to later full‐dose HgCl 2 ; we have studied the mechanism of this resistance. Brown Norway rats given low‐dose HgCl 2 showed only a modest increase in serum IgE level, three logs lower than rats given standard‐dose HgCl 2 , and no up‐regulation of splenic interleukin (IL)‐4 mRNA. There was up‐regulation of splenic interferon (IFN)‐γ gene expression and a progressive rise in serum IFN‐γ. Neither IL‐12 nor IL‐18 were induced, but there was up‐regulation of IL‐12 receptor β2‐chain (IL‐12Rβ2) expression. IL‐10 and transforming growth factor (TGF)‐β expression did not change. Serum IgE and splenic IL‐4 mRNA expression remained static when these rats were rechallenged, confirming resistance. Thereafter IFN‐γ expression gradually fell, after which IL‐4 expression and serum IgE rose slightly. Our observations suggest that low‐dose HgCl 2 confers protection in Brown Norway rats to further HgCl 2 by up‐regulation of IFN‐γ, associated with enhanced IL‐12Rβ2 expression. The immunological response to HgCl 2 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.