Effects of chronic exposure to DDT and TCDD on disease activity in murine systemic lupus erythematosus

Abstract

Oestrogens contribute to the female preponderance of autoimmune diseases such as systemic lupus erythematosus (SLE). Environmental xenoestrogens superimposed upon endogenous pituitary-gonadal axis may affect the development of autoimmunity. This study examined the effects of chronic exposure to xenoestrogens – o,p’-dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on disease activity in the New Zealand Black/New Zealand White F1 hybrid (B/W) mouse model of SLE. Intact female mice had repeatedly received injections of DDT, TCDD or control vehicle since 6 weeks of age. Weight change, albuminuria, mortality, relevant immunological and histological parameters were assessed. DDT exposure markedly increased the incidence of albuminuria and reduced uterine weight but had no measured effects on immunity or mortality in this study. TCDD-exposed mice had significantly lower incidence of albuminuria, serum anti-DNA antibody and total IgG levels, and mortality compared to controls. Also, TCDD group had significantly lower thymic and splenic weights, decreased percentages of CD4+CD8+ thymocytes and splenic CD4+ T cells, increased percentage of splenic B220+sIgM+ B cells and higher serum interferon gamma concentration. Taken together, DDT exposure appeared to accelerate the development of albuminuria in lupus-prone mice. TCDD was immunosuppressive to murine SLE. Xenoestrogens may have compound- and tissue-specific effects that require further elucidation in future work.