4.6 Article

Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 228, Issue 1, Pages 68-75

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2007.11.031

Keywords

trichloroethene (TCE); MRL plus / plus mice; cytokines; immunotoxicity; autoimmunity; hepatitis

Funding

  1. NIEHS NIH HHS [ES11584, R01 ES011584, P30ES06676, R01 ES011584-05, P30 ES006676] Funding Source: Medline

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Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice. (c) 2007 Elsevier Inc. All rights reserved.

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