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-tetrachlorodibenz o-p-dioxin (TCDD) on their immune system was investigated. Dietary adm inistration 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-dependen t reduction of in vitro lipopolysaccharide-induced production of inter leukin (IL)-1 in cultures of their splenic macrophages. A 30-day expos ure produced approximately 30% suppression and 180-day exposure produc ed approximately 52% suppression. This reduction did not negatively in fluence lipopolysaccharide-induced proliferation of B cells, instead a n enhancement of B cell proliferation was observed after 30 days expos ure. A 180 day exposure significantly suppressed the generation of IL- 2 by either concanavalin A or phorbol myristate acetate/calcium ionoph ore stimulation, and reduced the lectin-induced proliferation of splen ic T cells. The 30-day TCDD exposure showed no such immunotoxicity. TC DD at both exposure durations suppressed the expression of the alpha c hain 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 ce ll subsets, some of the immunotoxic effects being produced early, whil e others require a longer exposure period. The effect of TCDD on B cel ls appears to be of transient nature, with less potentially serious co nsequences. Such exposure also down-regulates the IL-1 production func tion 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.