TRICHLOROETHENE-INDUCED AUTOIMMUNE-RESPONSE IN FEMALE MRL-+ + MICE/

Trichloroethene (TCE) has been implicated in the pathogenesis of autoi mmune diseases such as systemic lupus erythematosus (SLE) and sclerode rma in humans. However, experimental studies have not been conducted t o establish the role of TCE in causing autoimmunity and/or SLE. To cla rify 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 meta bolites of TCE with strong acylating property), or an equal volume (10 0 mu l) of corn oil alone (controls). Animals were dosed every 4th day for 6 weeks and euthanized 24 hr following the last dose. Sera and ma jor tissues were collected and analyzed. Spleen weights in the TCE and DCAC groups increased 36% with a similar pattern of change in the spl een-to-body weight ratios. Serum IgG in the TCE and DCAC groups increa sed 45 and 322%, respectively. Using specific ELISA assays for mice, a utoimmune antibodies were detected in the sera of TCE- and DCAC-treate d mice in the following patterns: for anti-nuclear antibodies; control s, 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-sp ecific antibodies using conjugated DCAC-albumin as an antigen showed t he following pattern: for controls, 0/4; TCE, 0/4; DCAC, 5/5. These re sults suggest that TCE and its metabolite, DCAC, induce and/or acceler ate 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 a utoimmunity. (C) 1995 Academic Press, Inc.