Evidence of autoimmune-related effects of trichloroethylene exposure from studies in mice and humans

Abstract

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+/+ 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.

Figure 1

Association between risk of scleroderma and occupational exposure to TCE in men (A) and women (B), based on data from three case–control studies (Diot et al. 2002; Garabrant et al. 2003; Nietert et al. 1998). The graphics show the estimated measures of association from these studies. The pooled estimates are based on a meta-analysis using a random-effects model to include the possibility of nonrandom error between studies. Each square and corresponding line represent the OR and 95% CI from the individual study, with the relative size of the squares reflecting the relative weights of the studies. The horizontal midpoint of each diamond represents the pooled OR estimate and the horizontal extremes indicate the 95% CI.