Gilbert KM, Rowley B, Gomez-Acevedo H, Blossom SJ. Toxicol Sci. 2010 Nov 17. [Epub ahead of print]
Children's Hospital Research Institute, 13 Children's Way, Little Rock, AR 72202, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org.
We have shown previously that chronic (32-week) exposure to occupationally-relevant concentrations of the environmental pollutant trichloroethylene (TCE) induced autoimmune hepatitis in autoimmune-prone MRL+/+ mice. In real-life individuals are never exposed to only one chemical such as TCE. However, very little is known about the effects of chemical mixtures on the immune system. The current study examined whether co-exposure to another known immunotoxicant, mercuric chloride (HgCl(2)), altered TCE-induced autoimmune hepatitis. Female MRL+/+ mice were treated for only 8 weeks with TCE (9.9 or 186.9 mg/kg/day in drinking water) and/or HgCl(2) (260 μg/kg/day, sc). Unlike mice exposed to either TCE or HgCl(2) alone, mice exposed to both toxicants for 8 weeks developed significant liver pathology commensurate with early stages of autoimmune hepatitis. Disease development in the co-exposed mice was accompanied by a unique pattern of anti-liver and anti-brain antibodies that recognized, among others, a protein of approximately 90 kDa. Subsequent immunoblotting showed that sera from the co-exposed mice contained antibodies specific for HSP-90, a chaperone protein targeted by antibodies in patients with autoimmune hepatitis. Thus, although TCE can promote autoimmune disease following chronic exposure, a shorter exposure to a binary mixture of TCE and HgCl(2) accelerated disease development. Co-exposure to TCE and HgCl(2) also generated a unique liver-specific antibody response not found in mice exposed to a single toxicant. This finding stresses the importance of including mixtures in assessments of chemical immunotoxicity.