Lifetime exposure to trichloroethylene (TCE) does not accelerate autoimmune disease in MRL +/+ mice.
A genetically-prone murine lupus model was used to assess the developmental effects of trichloroethylene (TCE) exposure on disease symptom onset (e.g., autoantibody production and proteinuria), lymphocyte proliferation, splenic B-cell populations, and thymic and splenic T-cell populations. MRL +/+ mice were exposed to TCE (0, 1,400 or 14,000 ppb) via drinking water beginning on gestation day (GD) 0 and continuing until 12 months of age. With the exception of splenic CD4-/CD8-cells in female mice only, no alterations were observed in splenic T-cell populations, numbers of splenic B220+ cells, or in lymphocyte proliferation at 12 months of age. Furthermore, populations of all thymic T-cell subpopulations were decreased in male but not female mice following exposure to 14,000 ppb TCE. Autoantibody levels (anti-dsDNA and anti-GA) were assessed periodically from 4 to 12 months of age. Over this period, no increase in autoantibody levels as compared to control was detected, suggesting that TCE did not contribute to or accelerate the development of autoimmune disease markers following lifetime exposure. Not only does this study offer encouraging results, but it is the first study to approach the development of autoimmunity in a novel lifetime exposure paradigm, using an autoimmune prone model, at environmentally relevant exposure levels.
Peden-Adams
Margie M
MM
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29412, USA. pedenada@musc.edu
Eudaly
Jackie G
JG
Lee
A Michelle
AM
Miller
Julie
J
Keil
Deborah E
DE
Gilkeson
Gary S
GS
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005838:Genotype; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014241:Trichloroethylene / Q000633:toxicity*
D001323:Autoantibodies; D014241:Trichloroethylene