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

Abstract

ObjectiveOur objective was to examine experimental and epidemiologic studies pertaining to immune-related, and specifically autoimmune-related, effects of trichloroethylene (TCE).Data sources and extractionWe 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 synthesisStudies 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-γ (IFN-γ) 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-γ 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.ConclusionThe 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.

Dysregulation of the immune system caused by silica and asbestos

“…Silica is considered one of the most important environmental substances, in the fashion of vinyl chloride and other chemicals (including trichloroethene and epoxy resins), that give rise to autoimmune diseases in exposed hosts (Trice and Pinals, 1985;Goldman, 1996;D'Cruz, 2000;Hess, 2002;Cooper et al, 2009).…”

Suppression of pulmonary host defenses and enhanced susceptibility to respiratory bacterial infection in mice following inhalation exposure to trichloroethylene and chloroform

“…There is very limited information on the effects of either TCE or chloroform on immune responses and host resistance to infection although the relationship between TCE exposure and autoimmune disease is well-established (Cooper et al, 2009). Studies using traditional measures to assess systemic effects on the immune system (Luster et al, 1988) suggested that oral exposure to TCE suppresses immune responses in weanling mice (Sanders et al, 1982) and in offspring following gestational exposure (Peden-Adams et al, 2006).…”

Upregulation of Calprotectin and Downregulation of Retinol Binding Protein in the Serum of Workers with Trichloroethylene‐induced Hypersensitivity Dermatitis

“…In the past 10 yr, an increasing number of cases suffering from TCE-induced hypersensitivity dermatitis (THD) have been reported in Guangdong Province in southern China 3) . Concern that TCE may exert immunotoxic effects 7) has driven epidemiological and experimental studies investigating TCE exposure and risk of THD. The genetic polymorphism of human leukocyte antigen HLA-B*1301 is strongly associated with THD among exposed workers and might be used as a biomarker to predict high-risk individuals exposed to TCE 8) .…”