Trichloroethene-induced autoimmune response in female MRL +/+ mice.
Trichloroethene (TCE) has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental studies have not been conducted to establish the role of TCE in causing autoimmunity and/or SLE. To clarify the role of TCE in autoimmune responses, subchronic studies were carried out in female autoimmune prone mice (MRL +/+). Three groups of mice (5 weeks old) received intraperitoneal injections of 10 mmol/kg of TCE, 0.2 mmol/kg of dichloroacetyl chloride (DCAC) (one of the metabolites of TCE with strong acylating property), or an equal volume (100 microliters) of corn oil alone (controls). Animals were dosed every 4th day for 6 weeks and euthanized 24 hr following the last dose. Sera and major tissues were collected and analyzed. Spleen weights in the TCE and DCAC groups increased 36% with a similar pattern of change in the spleen-to-body weight ratios. Serum IgG in the TCE and DCAC groups increased 45 and 322%, respectively. Using specific ELISA assays for mice, autoimmune antibodies were detected in the sera of TCE- and DCAC-treated mice in the following patterns: for anti-nuclear antibodies; controls, 0/4; TCE, 4/4; DCAC, 3/5; for anti-ssDNA antibodies; controls, 0/4; TCE, 2/4; DCAC, 5/5; for anti-cardiolipin antibodies; controls, 0/4; TCE, 0/4; DCAC, 3/5. An ELISA developed for the measurement of DCAC-specific antibodies using conjugated DCAC-albumin as an antigen showed the following pattern: for controls, 0/4; TCE, 0/4; DCAC, 5/5. These results suggest that TCE and its metabolite, DCAC, induce and/or accelerate autoimmune responses in female MRL +/+ mice. The greater responses induced by DCAC at a dose 50 times lower than TCE suggests that this metabolite may be important in the mechanisms leading to TCE-induced autoimmunity.
Khan
M F
MF
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Kaphalia
B S
BS
Prabhakar
B S
BS
Kanz
M F
MF
Ansari
G A
GA
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D015551:Autoimmunity / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D062845:Chloroacetates; D003999:Dichloroacetic Acid / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology; D014241:Trichloroethylene / Q000276:immunology* / Q000494:pharmacology
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D062845:Chloroacetates; D014241:Trichloroethylene; D003999:Dichloroacetic Acid