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 micrograms/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 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.
Badesha
J S
JS
Environmental Toxicology Centre, Faculty of Medicine, University of Bristol, Langford, UK.
Maliji
G
G
Flaks
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects
D007375:Interleukin-1; D007376:Interleukin-2; D007476:Ionophores; D008070:Lipopolysaccharides; D008934:Mitogens; D000072317:Polychlorinated Dibenzodioxins; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D013755:Tetradecanoylphorbol Acetate