title: 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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC 20460 , USA. cooper.glinda@epa.gov
authors.forename: Glinda S
authors.initials: GS
authors.lastname: Cooper
authors.forename: Susan L
authors.initials: SL
authors.lastname: Makris
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nietert
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jinot
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000378:metabolism; D004781:Environmental Exposure; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D015847:Interleukin-4; D014241:Trichloroethylene; D007371:Interferon-gamma