THE EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON TUMOR-NECROSIS-FACTOR (TNF) PRODUCTION BY PERITONEAL-CELLS

Recent studies in mice have demonstrated that TNF plays a critical rol e in mediating the TCDD-induced enhanced inflammatory response to intr aperitoneal (i.p.) sheep red blood cells. The current studies were des igned to evaluate the effects of TCDD on TNF production by ex-vivo per itoneal cells and a peritoneal macrophage cell line (IC-21) stimulated with LPS. In support of the hypothesis that TCDD can act directly on the peritoneal macrophage to increase TNF production, following pretre atment with TCDD, both ex-vivo peritoneal cells and IC-21 cells produc ed increased levels of bioactive TNF when stimulated with LPS. Flow cy tometric analyses of IC-21 cells indicate that TCDD exposure increases intracellular production and secretion of TNF but does not alter leve ls of membrane associated TNF. (C) 1997 Elsevier Science Ireland Ltd.