Dental amalgam fillings are the most important source of
mercury exposure in the general population, but their potential to cause systemic health consequences is disputed. In this study, inbred mice genetically susceptible to
mercury-induced immune aberrations were used to examine whether
dental amalgam may interfere with the immune system and cause autoimmunity. Female SJL/N mice were implanted in the peritoneal cavity with 8-100 mg
silver amalgam or
silver alloy for 10 weeks or 6 months. Chronic
hyperimmunoglobulinemia, serum
IgG autoantibodies targeting the
nucleolar protein fibrillarin, and systemic
immune-complex deposits developed in a time- and dose-dependent manner after implantation of amalgam or
alloy. Splenocytes from mice implanted with amalgam or
alloy showed an increased expression of class II molecules. The functional capacity of splenic T and B cells was affected in a dose-dependent way: 10 weeks of low-dose and 6 months of high-dose amalgam implantation strongly increased
mitogen-induced T and B cell proliferation, whereas 10 weeks of high-dose implantation decreased the proliferation. Not only
mercury but also
silver accumulated in the spleen and kidneys after amalgam implantation. In conclusion,
dental amalgam implantation in a physiological body milieu causes chronic stimulation of the immune system with induction of systemic autoimmunity in genetically sensitive mice. Implantation of
silver alloy not containing
mercury also induced autoimmunity, suggesting that other elements, especially
silver, have the potential to induce autoimmunity in genetically susceptible vertebrates. Accumulation of
heavy metals, from
dental amalgam and other sources, may lower the threshold of an individual
metal to elicit immunological aberrations. We hypothesize that under appropriate conditions of
genetic susceptibility and adequate body burden,
heavy metal exposure from
dental amalgam may contribute to immunological aberrations, which could lead to overt autoimmunity.