IMMUNOTOXIC EFFECTS OF PROLONGED DIETARY EXPOSURE OF MALE-RATS TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

The effects of low level exposure of rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on their immune system was investigated. Dietary administration to young adult male Leeds strain rats of a total dose of 3 mu g/kg body weight of TCDD resulted in an exposure duration-dependent reduction of in vitro lipopolysaccharide-induced production of interleukin (IL)-1 in cultures of their splenic macrophages. A 30-day exposure produced approximately 30% suppression and 180-day exposure produced approximately 52% suppression. This reduction did not negatively influence lipopolysaccharide-induced proliferation of B cells, instead an enhancement of B cell proliferation was observed after 30 days exposure. A 180 day exposure significantly suppressed the generation of IL-2 by either concanavalin A or phorbol myristate acetate/calcium ionophore stimulation, and reduced the lectin-induced proliferation of splenic T cells. The 30-day TCDD exposure showed no such immunotoxicity. TCDD at both exposure durations suppressed the expression of the alpha chain of the IL-2 receptor in concanavalin A-activated T cells, without affecting the CD4(+)/CD8(+) ratio. The results suggest that exposure to a low dietary dose of TCDD suppresses the functions of several T cell subsets, some of the immunotoxic effects being produced early, while others require a longer exposure period. The effect of TCDD on B cells appears to be of transient nature, with less potentially serious consequences. Such exposure also down-regulates the IL-1 production function of macrophages. A common mechanism of TCDD immunotoxicity may be on the multifunctional signal transduction pathways downstream to the activation of protein kinase C and Ca2+ flux.