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

Abstract

Experimental models of chemically induced autoimmunity have contributed to our understanding of the development of autoimmune diseases in humans. Heavy metals such as mercury induce a dramatic activation of the immune system and autoantibody production in genetically susceptible rats and mice. This autoimmune syndrome is dependent on T cells, which are important for B-cell activation and cytokine secretion. Several studies have focused on the roles of T-helper (Th)1 and Th2 cells and their respective cytokines in the pathogenesis of mercury-induced disease. This article reviews recent studies that have examined the patterns of cytokine gene expression and where investigators have manipulated the Th1 and Th2 responses that occur during mercury-induced autoimmunity. Finally, we will discuss some biochemical/molecular mechanisms by which heavy metals may induce cytokine gene expression.

Exposure to mercuric chloride during the induction phase and after the onset of collagen‐induced arthritis enhances immune/autoimmune responses and exacerbates the disease in DBA/1 mice

“…the early up-regulation of interleukin (IL)-2 and interferon-c (IFN-c), followed by pronounced expression of IL-4 mRNA, 15 thereby giving rise to a T helper 2 (Th2) type of autoimmune response. 5 As the spontaneous development of autoimmune disease in humans and animal models is also thought to involve genetic predisposition and immune dysregulation, [16][17][18] our hypothesis was that the immunotoxicity of mercury might be more pronounced in individuals predisposed to spontaneous development of autoimmune disease. 19 Upon exposing young (NZB · NZW) F1 hybrid and tight skin 1 (Tsk1) mice, which are genetically prone to develop diseases resembling systemic lupus erythematosus and scleroderma, respectively, to mercury, we observed potent and characteristic immune/autoimmune activation in both strains.…”

“…High titres of IgG ANolAs, the hallmark of mercury‐induced autoimmunity in susceptible mice, 4,5 , 7,9 , 11 , 11–13,19 can be detected 2 weeks after treatment 19 and persist in certain strains for approximately 12 months, i.e. several months after the cessation of mercury treatment 39 .…”

“…Exposure of various mammalian species – including humans, rabbits, rats and mice – to mercurial compounds can give rise to immunosuppression and/or autoimmunity 1–4 . The autoimmune effects of, in particular, inorganic mercury salts have been extensively characterized in susceptible rodent strains 3–6 . In susceptible mice, for example, such autoimmunity involves the polyclonal activation of B cells by CD4 + T cells, increased serum levels of immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), the production of antibodies with different specificities [in particular, anti‐nucleolar autoantibodies (ANolA)] and the formation of renal deposits of IgG 7–10 …”

“…Moreover, the exposure of susceptible mice to mercury has been reported to result in the aberrant production of various cytokines – i.e. the early up‐regulation of interleukin (IL)‐2 and interferon‐γ (IFN‐γ), followed by pronounced expression of IL‐4 mRNA, 15 thereby giving rise to a T helper 2 (Th2) type of autoimmune response 5 …”

“…[1][2][3][4] The autoimmune effects of, in particular, inorganic mercury salts have been extensively characterized in susceptible rodent strains. [3][4][5][6] In susceptible mice, for example, such autoimmunity involves the polyclonal activation of B cells by CD4 + T cells, increased serum levels of immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), the production of antibodies with different…”