TUMOR-NECROSIS-FACTOR INVOLVEMENT IN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN-MEDIATED ENDOTOXIN HYPERSENSITIVITY IN C57BL/6J MICE CONGENIC AT THE AH LOCUS

An experimental model of endotoxin-induced release of tumor necrosis factor-α (TNF) into the serum of C57BL 6J mice congenic at the Ah locus was used to investigate the effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on TNF production. TCDD exposure of Ah-responsive mice (Ahbb) resulted in a dose-dependent increase in the concentration of TNF in the serum of endotoxin-exposed mice, with a significant increase observed at a dose of 10 μg/kg TCDD. At a dose of 500 μg/kg TCDD, Ahbb mice demonstrated a 46-fold increase in serum TNF levels compared to control. In contrast, congenic Ah-receptor deficient mice (Ahdd) did not show a significant increase in serum TNF levels until exposed to 150 μg/kg TCDD, and the maximum response was an 8-fold increase over control. These data suggest that increased TNF production may be responsible for endotoxin hypersensitivity in TCDD-treated mice and that the Ah locus mediates this response. © 1991.