Long-term orally exposure of dioxins affects antigen-specific antibody production in mice.

Dioxins are persistent environmental toxins that are still present in the food supply despite strong efforts to minimize exposure. Dioxins ingested by humans accumulate in fat and are excreted very slowly, so their long-term effects at low concentrations are a matter of concern. It is necessary to consider long-term, low-dose continuous administration under conditions that are as close as possible to a person's diet. In this study, we orally administered 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), the most common dioxin, at low doses in mice and observed the immunological effects. We found that antigen-specific (OVA) antibody production in the serum increased dose-dependently by TCDD concentrations below 500 ng/kg after long-term (10 weeks) exposure. Similar increases were seen in fecal and vaginal samples but were not significant. Th1 and Th2 lymphocyte responses, as determined by antibody and cytokine production, also significantly increased dose-dependently up to 500 ng/kg TCDD, and the Th1/Th2 balance was shifted toward Th1. These results indicate that low-dose, long-term TCDD exposure results in immunological abnormalities, perhaps by increasing antigen permeability. Different doses of dioxins may have opposing effects, being immunostimulatory at low doses (100 ng/kg/day) and immunosuppressive at high doses (500 ng/kg/day).