Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus

Charles S. Via, Phuong Nguyen, Florin Niculescu, John Papadimitriou, Dennis Hoover, Ellen K. Silbergeld

Research output: Contribution to journalArticlepeer-review

Abstract

Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 μg/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

Original languageEnglish (US)
Pages (from-to)1273-1277
Number of pages5
JournalEnvironmental health perspectives
Volume111
Issue number10
DOIs
StatePublished - Aug 1 2003

Keywords

  • Autoimmunity
  • Glomerulonephritis
  • Graft-versus-host-disease
  • Lupus
  • Mercury
  • T cells

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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