Thiol compounds inhibit mercury-induced immunological and immunopathological alterations in susceptible mice

Abstract

SUMMARYIn vitro mercury induces a high proliferative response in splenic lymphocytes and in vivo it induces a systemic autoimmune disease in susceptible mouse strains. This disease is characterized by increased serum levels of IgE and IgG1 antibodies, by the production of anti-nucleolar antibodies and by the formation of renal immune complex deposits. We have previously found that the presence of 2-mercaptoethanol (2-ME) inhibited mercury-induced cell proliferation in vitro. In this study, we tested the effects of four other thiol compounds, namely dithiothreitol (DTT), L-cysteine, meso-2,3-dimercaptosuccinic acid (meso-DMSA) and 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS) on mercury-induced immunological changes both in vitro and in vivo. We found that in vitro, the addition of all thiol compounds abrogated mercury-induced cell aggregation and proliferation. In vivo, injection of meso-DMSA and/or DMPS (s.c. or i.p.) immediately following exposure to mercury markedly decreased IgG1 synthesis in spleen cells and serum IgE levels in mercury-susceptible SJL mice. Treatment with DMPS also prevented mercury-induced IgG1 anti-nucleolar antibody synthesis and the development of mesangial IgG1 immune complex deposits in SJL mice.

Cytokine Regulation of a Rodent Model of Mercuric Chloride-Induced Autoimmunity

“…Because mercury has a strong affinity for thiol groups, it is possible that mercury may bind intracellular thiols, resulting in decreased thiol levels and a shift toward a Th2 profile in susceptible animals. Supporting this hypothesis, administration of thiol compounds in mice prevents development of mercuryinduced IgGI ANoA and IgG1 immune complexes and reduces serum IgE levels in SJL mice (60 (1,61,62). Further studies are also needed to clearly elucidate the pattern of cytokine expression in this syndrome and to determine their exact requirement for disease development.…”

Cytokine regulation of a rodent model of mercuric chloride-induced autoimmunity.

“…Because mercury has a strong affinity for thiol groups, it is possible that mercury may bind intracellular thiols, resulting in decreased thiol levels and a shift toward a Th2 profile in susceptible animals. Supporting this hypothesis, administration of thiol compounds in mice prevents development of mercuryinduced IgGI ANoA and IgG1 immune complexes and reduces serum IgE levels in SJL mice (60). Strain differences in intracellular thiol levels may contribute to the differential responses elicited by HgCl2 in either resistant or susceptible animals, thus explaining predominantly Thl or Th2 patterns of cytokine expression.…”

How can a chemical element elicit complex immunopathology? Lessons from mercury-induced autoimmunity

“…The high affinity of the metal for thiol-containing molecules can alter the availability of such species to immune cells [84]. GSH, the most abundant source of intracellular thiols, imparts changes in patterns of cytokine expression.…”