Academic journal article Environmental Health Perspectives

Evidence of Autoimmune-Related Effects of Trichloroethylene Exposure from Studies in Mice and Humans

Academic journal article Environmental Health Perspectives

Evidence of Autoimmune-Related Effects of Trichloroethylene Exposure from Studies in Mice and Humans

Article excerpt

OBJECTIVE: Our objective was to examine experimental and epidemiologic studies pertaining to immune-related, and specifically autoimmune-related, effects of trichloroethylene (TCE).

DATA SOURCES AND EXTRACTION: We performed a literature search of PubMed and reviewed bibliographies in identified articles. We then systematically reviewed immune-related data, focusing on clinical and immunologic features and mechanistic studies.

DATA SYNTHESIS: Studies conducted in [MRL.sup.+/+] lupus mice report an accelerated autoimmune response in relation to exposure to TCE or some metabolites. Effects have been reported after 4 weeks of exposure to TCE at doses as low as 0.1 mg/kg/day in drinking water and have included increased antinuclear antibodies and interferon - [gamma] (IFN-[gamma]) and decreased secretion of interleukin-4 (IL-4), consistent with an inflammatory response. Autoimmune hepatitis, inflammatory skin lesions, and alopecia have been found after exposures of 32-48 weeks. Recent mechanistic experiments in mice examined oxidative stress and, specifically, effects on lipid-peroxidation-derived aldehydes in TCE-induced autoimmune disease. Two studies in humans reported an increase in IL-2 or IFN-[gamma] and a decrease in IL-4 in relation to occupational or environmental TCE exposure. Occupational exposure to TCE has also been associated with a severe, generalized hypersensitivity skin disorder accompanied by systemic effects, including hepatitis. In three case-control studies of scleroderma with a measure of occupational TCE exposure, the combined odds ratio was 2.5 [95% confidence interval (CI), 1.1-5.4] in men and 1.2 (95% CI, 0.58-2.6) in women.

CONCLUSION: The consistency among the studies and the concordance between the studies in mice and humans support an etiologic role of TCE in autoimmune disease. Multisite collaborations and studies of preclinical immune markers are needed to further develop this field of research.

KEYWORDS: autoimmune liver disease, solvents, systemic sclerosis, trichloroethylene. Environ Health Perspect 117:696-702 (2009). doi:10.1289/ehp.11782 available via http://dx.doi.org/ [Online 9 January 2009]

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Trichloroethylene (TCE) is an industrial solvent that has been used extensively in industrial operations involving metal cleaning and degreasing. Its metabolism through a cytochrome P450 (CYP) pathway involving the enzyme CYP2E1 results in numerous metabolites, including chloral, chloral hydrate, dichloroacetic acid, trichloracetic acid, trichloroethanol, and trichloroethanol glucuronide (Lash et al. 2000). Many studies of immune-related effects of TCE have been conducted in the past decade, with much of this work focusing on autoimmune disease. We reviewed this recent research to determine the strength and consistency of data from experimental and epidemiologic studies, and the concordance between human and animal data, pertaining to these effects.

Materials and Methods

We searched PubMed (National Center for Biotechnology Information 2008) for studies related to TCE and immune effects, using forms of "immune," "autoimmune," "immunosuppression," "cytokines," "lupus," "scleroderma," "rheumatoid arthritis," "vasculitis," and "liver" as search terms. We also reviewed references within relevant reports, including the National Academy of Sciences 2006 report on TCE (National Research Council 2006). We did not include studies of in utero or developmental exposures (Blossom and Doss 2007; Blossom et al. 2007; PedenAdams et al. 2006, 2008) in this review.

We abstracted data pertaining to immunosuppression, hypersensitivity, and autoimmune-related effects, including clinically expressed or clinically diagnosed disease, cytokine expression or levels, T-cell activation, and serology [antinuclear antibodies (ANA) and specific autoantibodies]. We present, in tabular form, end points that all, or almost all, of the identified reports examined and include information on both "positive" and "negative" effects found in the studies. …

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