Objective To examine effects of the environmental xenoestrogens o,p'-dichlorodiphenyltrichloroethane (DDT) and tetrachlorodibenzodioxin (TCDD) on development of autoimmunity in the female NZB x NZW F1 (B/W) mouse model of lupus.
Methods Development of murine lupus was assessed during the lifespan female B/W mice given 3.2 μg of DDT (n = 13) or TCDD (n = 13) compared to female B/W mice given vehicle (n = 13). At 8-week intervals, mice were examined for weight change, albuminuria, antibodies to DNA, and IgG immunoglobulin levels, morbidity, and mortality. Parallel groups of mice were examined for thymic/splenic histopathology and CD4/CD8 ratio.
Results The administration of DDT or TCDD was well tolerated without apparent side effects. Weight gain in exposed B/W mice and control mice was identical through 32 weeks of age. In DDT-exposed female B/W mice, the development of albuminuria was accelerated compared to control mice, but there was no significant effect on total IgG, anti-DNA antibodies, thymic/splenic cellularity, or mortality. In contrast, TCDD-exposed B/W mice had lower total IgG concentrations, significantly lower levels of anti-DNA (p < .05), lower incidence of albuminuria, significantly lower thymic and splenic weight and cellularity (p < .05), decreased CD4/CD8 ratio, and markedly reduced mortality compared to control and DDT exposed B/W mice (p < .05).
Conclusion The environmental xenoestrogen DDT increased the incidence of albuminuria in lupus-prone mice but did not significantly alter other disease parameters or mortality. In contrast, TCDD, a different environmental estrogen, suppressed markers of autoimmunity and the development of autoimmune glomerulonephritis compared to control mice. These results suggest that environmental estrogens, at molar concentrations similar to endogenous 17β-estradiol, do not markedly accelerate autoimmunity, and, in the case of TCDD, are immunosuppressive, either through a direct immunotoxic effect on thymus and spleen or indirectly through hormonal mechanisms. Further studies of dose-response relationships, specific mechanisms, and synergistic effects may elucidate environmental influences on human SLE and immune response.
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