Mercury inducing disease in animal experiments

"Thimerosol is the preservative in immunisation shots, so anytime you get an immunisation shot you are undergoing the same procedure that in the University Lab that we used to give animals auto-immune disease---give a little tiny injection of mercury.  And when you get an immunisation shot you are getting a little tiny dose of mercury there."---Hal Huggins DDS

Bigazzi PE.        Metals and Kidney Autoimmunity.Environ Health Perspect. 1999 Oct;107(Suppl 5):753-765.[Record as supplied by publisher]PMID: 10502542.
The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity.
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Bernaudin JF, Druet E, Druet P, Masse R.Inhalation or ingestion of organic or inorganic mercurials produces auto-immune disease in rats.Clin Immunol Immunopathol. 1981 Jul;20(1):129-35. No abstract available.PMID: 7021027 [PubMed - indexed for MEDLINE]

Pollard KM, et al.  Lupus-Prone Mice as Models to Study Xenobiotic-Induced Acceleration of Systemic Autoimmunity.Environ Health Perspect. 1999 Oct;107(Suppl 5):729-735.[Record as supplied by publisher]PMID: 10502538.         [See Related Articles]

The linkage between xenobiotic exposures and autoimmune diseases remains to be clearly defined. However, recent studies have raised the possibility that both genetic and environmental factors act synergistically at several stages or checkpoints to influence disease pathogenesis in susceptible populations. These observations predict that individuals susceptible to spontaneous autoimmunity should be more susceptible following xenobiotic exposure by virtue of the presence of predisposing background genes. To test this possibility, mouse strains with differing genetic susceptibility to murine lupus were examined for acceleration of autoimmune features characteristic of spontaneous systemic autoimmune disease following exposure to the immunostimulatory metals nickel and mercury. Although NiCl(subscript)2(/subscript) exposure did not exacerbate autoimmunity, HgCl(subscript)2(/subscript) significantly accelerated systemic disease in a strain-dependent manner. Mercury-exposed (NZB X NZW)F(subscript)1(/subscript) mice had accelerated lymphoid hyperplasia, hypergammaglobulinemia, autoantibodies, and immune complex deposits. Mercury also exacerbated immunopathologic manifestations in MRL+/+ and MR (italic)-lpr (/italic)mice. However, there was less disease acceleration in (italic)lpr(/italic) mice compared with MRL+/+ mice, likely due to the fact that environmental factors are less critical for disease induction when there is strong genetic susceptibility. Non-major histocompatability complex genes also contributed to mercury-exacerbated disease, as the nonautoimmune AKR mice, which are H-2 identical with the MRL, showed less immunopathology than either the MRL/(italic)lp(/italic)r or MRL+/+ strains. This study demonstrates that genetic susceptibility to spontaneous systemic autoimmunity can be a predisposing factor for HgCl(subscript)2(/subscript)-induced exacerbation of autoimmunity. Such genetic predisposition may have to be considered when assessing the immunotoxicity of xenobiotics. Additional comparative studies using autoimmune-prone and nonautoimmune mice strains with different genetic backgrounds will help determine the contribution that xenobiotic exposure makes in rendering sensitive populations susceptible to autoimmune diseases.

Bagenstose LM, et al.       Murine mercury-induced autoimmunity: a model of chemically related autoimmunity in humans.Immunol Res. 1999;20(1):67-78. Review.PMID: 10467984; UI: 99396060.    [See Related Articles]

Human exposure to certain compounds or therapeutic drugs can result in the development of an autoimmune syndrome. Mercury (Hg) induced autoimmunity is one of the few animal models in which administration of a chemical induces a specific loss of tolerance to self-antigens. After receiving subtoxic doses of Hg or other heavy metals, susceptible mouse strains rapidly develop highly specific antibodies to nucleolar antigens. In addition, these animals display a general activation of the immune system, especially pronounced for the Th2 subset and a transient glomerulonephritis with immunoglobulin deposits. Like many human autoimmune diseases, this syndrome is associated with the expression of susceptible major histocompatibility complex (MHC) class II genes. In this article, we review the essential features of this model, and we discuss the putative mechanisms by which Hg creates such a severe immune dysfunction.

Kubicka-Muranyi M, et al.     
Murine systemic autoimmune disease induced by mercuric chloride (HgCl2): Hg-specific helper T-cells react to antigen stored in macrophages.Int J Immunopharmacol. 1993 Feb;15(2):151-61.PMID: 8468118; UI: 93224224.
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Hultman P, et al.    Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease.Toxicol Appl Pharmacol. 1992 Apr;113(2):199-208.PMID: 1532866; UI: 92221384.       [See Related Articles]