DEVELOPMENTAL EXPOSURE TO LEAD CAUSES PERSISTENT IMMUNOTOXICITY IN FISCHER-344 RATS

Lead has been shown to exert toxic effects during early development. I n these in vivo and ex vivo experiments, the effect of lead on the imm une system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 p pm lead) in their drinking water during breeding and pregnancy (exposu re was discontinued at parturition), Offspring received no additional lead treatment after birth. Immune function was assessed in female off spring at 13 weeks of age. Dams in lead-exposed groups were not differ ent from controls with respect to the immune endpoints used in these e xperiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effecto r function properties (tumor necrosis factor-alpha and nitric oxide pr oduction) were elevated in the 250 ppm group, while cell-mediated immu ne function was depressed, as shown by a decrease in delayed-type hype rsensitivity reactions in the 250 ppm group. Interferon-gamma levels w ere decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate tha t exposure of mothers to moderate levels of lead produces chronic immu ne modulation in their F344 rat offspring exposed in utero, Since the mothers were not susceptible to chronic immune alterations, a developm ental bias to the immunotoxic effects of lead is indicated, The differ ences observed are consistent with the possibility that lead may bias T helper subset development and/or function, resulting in alterations in the balance among type 1 and type 2 immune responses, (C) 1998 Soci ety of Toxicology.