TUMOR-NECROSIS-FACTOR INVOLVEMENT IN THE TOXICITY OF TCDD - THE ROLE OF ENDOTOXIN IN THE RESPONSE

We have previously demonstrated that tumor necrosis factor is involved in the acute toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TC DD), since therapies designed to attenuate the effects of tumor necros is factor resulted in reduced mortality and toxicity in mice exposed t o an LD(75) dose of TCDD. The current study addresses whether endotoxi n may be a contributing factor in the cachexia and mortality resulting from TCDD exposure. Endotoxin-nonresponsive C3H/HeJ mice and endotoxi n-responsive C57BL/6 mice were treated with 350 mu g/kg TCDD and body weight and mortality were recorded. C3H/HeJ mice showed no trend in bo dy weight loss (p = 0.554), while C57BL/6 mice demonstrated a statisti cally significant (p < 0.01) linear decline in body weight of -0.23 g/ day, resulting in a net loss of 3.5 g over 15 days preceding mortality . Mortality was observed in the C57BL/6 mice beginning on day 16 with 100% of the mice dying by the 23rd day while no mortality was observed in C3H/HeJ mice until the 24th day of the study with only 22% mortali ty observed. These data further demonstrate that endotoxin is a contri buting factor to the cachexia and lethality of TCDD.