Laboratory studies on the immune effects of halogenated aromatics

Abstract

The effects of TCDD exposure on the developing immune system were investigated in Wistar/Fischer hybrid or Fischer rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 muk/kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats was exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group 2). Variable but significant effects on body weights and thymus/body weight ratios were found up to 133 days of age. Cell mediated immune functions were depressed up to 133 days of age in both groups but less severely in animals exposed only postnatally. Furthermore, TCDD suppressed cell-mediated immune functions without affecting humoral immune function. Adoptive cell transfer studies indicated suppression of T-cell functions was selective in that "helper" cell function was not suppressed. In other studies, the effects on lymphocyte function following brief exposure of spleens from B6C3F1 mice to TCDD in dimethylsulfoxide (DMSO) were investigated. DNA, RNA and protein synthesis were inhibited at concentrations less than 2 X 10(-7) M TCDD in DMSO. This concentration accounted for approximately 0.2 ng TCDD uptake per spleen. The structurally related chemicals 3,4,3',4'-tetrachlorobiphenyl and 1-amino, 3,7,8-trichlorodibenzop-p-dioxin did not show significant lymphocyte effects even at two-fold higher concentrations. The ability of lymphocyte mitogens to bind to their cell surface receptors was not affected by TCDD treatment. TCDD was slightly cytolytic to lymphocytes after 48 hours of culture. DMSO treatment alone was also slightly toxic to lymphoid cells as indicated by a 10--20% loss of cell viability, although this occurred within 4 hours after DMSO exposure. Studies were performed to investigate the effects of 2,3,7,8-tetrachlorodibenzofuran (TCDF) on immune function in adult Hartley guinea pigs. Animals received 6 weekly doses of either 0, 0.05, 0.17, 0.5 or 1.0 microgram TCDF/kg body weight. TCDF slightly depressed cell-mediated immune functions, particularly at the higher dose levels as indicated by decreased lymphocyte blastogenesis, delayed hypersensitivity reactions, and production of macrophage inhibitor factor. Additionally, thymus-to-body-weight ratios were slightly reduced in the 0.5 and 1.0 microgram dosage groups. Serum IgG levels and antibody titer to BGG did not differ from controls. These results indicate that TCDF-induced immunosuppression is similar to that of TCDD.