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Setting the stage for illness: mercury exposure and autoimmune disease.

The current scientific literature abounds with studies of the strongly suspected link between exposure to inorganic mercury (iHg) and autoimmune disease, a family of often debilitating and sometimes fatal conditions. Although no human association has been documented, the connection is well known in animal models. A great deal of work continues to characterize the complex physiologic mechanisms involved and thereby shed light on the role of environmental mercury exposures in the etiology of these illnesses. Now a team of Maryland investigators has found that even brief, low-level environmental mercury exposure may increase susceptibility to autoimmune disease in mice [EHP 111:1273-1277].

iHg experiments often use mice bred for susceptibility to various autoimmune diseases. In this study, however, the team used healthy, genetically nonsusceptible mice. The researchers injected treatment groups of 6- to 8-week-old female B6D2[F.sub.1] mice with iHg doses of 20 or 200 micrograms per kilogram dissolved in water. The mice were dosed every other day for 15 days, for a total of 8 doses. Control animals were injected with an equal total volume of sodium chloride. Five days after cessation of the iHg injections, both case and control mice were intravenously administered spleen cells from another mouse strain to induce chronic graft-versus-host disease (GVHD), a well-established murine model of acquired autoimmunity.

This study involved very low exposures compared to those commonly used in studies of iHg immunotoxicity (typically 500-2,000 micrograms per kilogram). These low doses helped avoid confounding of the subsequent results by the toxic effects of iHg exposure itself or by directly causing iHg-associated autoimmune disease.

The dose of parental donor cells was set just above the threshold for consistent induction of chronic GVHD, and under normal conditions would be expected to induce a mild case of the lupuslike condition, as it did in the controls. In the case mice, however, the scientists determined that the iHg pretreatment clearly accelerated and exacerbated the course of the disease.

Unlike the control mice, the iHg-exposed mice experienced glomerulonephritis (an inflammatory kidney disease) and elevated urine protein, evidence of accelerated GVHD. The glomerulonephritis, in turn, resulted in accelerated mortality in the iHg-treated groups. Upon reexamination 2-3 months after disease induction, autoantibodies characteristic of chronic GVHD were found to have become significantly elevated in surviving iHg-treated mice, but no markers characteristic of iHg-associated autoimmunity were seen. These results imply that the iHg treatment affected the acquired autoimmune disease itself--that the disease was not caused by delayed effects of the iHg exposure, but that its course was worsened by the exposure.

The results of the study, the first of its kind, support the hypothesis that low-level environmental exposure to mercury is a potential factor in the development of autoimmune disease in humans. Disturbingly, these results further suggest that "low-level exposure ... may lower the threshold for disease development in susceptible individuals who later encounter the appropriate infectious or toxic triggers of disease." If these findings are confirmed by replication and further research, the implications regarding safe thresholds for environmental mercury exposure could be profound.
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Title Annotation:Science Selections
Author:Hood, Ernie
Publication:Environmental Health Perspectives
Date:Aug 1, 2003
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