Developmental Exposure to Lead Causes Persistent Immunotoxicity in Fischer 344 Rats

Abstract

Lead has been shown to exert toxic effects during early development. In these in vivo and ex vivo experiments, the effect of lead on the immune system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water during breeding and pregnancy (exposure was discontinued at parturition). Offspring received no additional lead treatment after birth. Immune function was assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were not different from controls with respect to the immune endpoints used in these experiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effector function properties (tumor necrosis factor-alpha and nitric oxide production) were elevated in the 250 ppm group, while cell-mediated immune function was depressed, as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm group. Interferon-gamma levels were decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate that exposure of mothers to moderate levels of lead produces chronic immune modulation in their F344 rat offspring exposed in utero. Since the mothers were not susceptible to chronic immune alterations, a developmental bias to the immunotoxic effects of lead is indicated. The differences 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.

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

“…The primary effect on T cells is a shift in the T helper (Th) cell functional balance, with Thl function depressed and Th2 function elevated (15). In a dose-response comparison among pregnant rats and rat female pups exposed during gestation and assessed as young adults, developing fetuses were susceptible to persistent immunotoxic effects of lead at doses that did not affect the pregnant dams (21,22). The nature of the immunotoxicity was similar to that reported for exposed adults; rats exposed in utero exhibited depressed Th 1 function (e.g., reflected by a depressed DTH response) with a concomitant elevation in some Th2-dependent parameters.…”

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema

“…Also, it has been suggested that zinc deficiency may promote T-helper (Th) type 2 cytokine responses [11]. In contrast, evidence in animals suggests that high exposure to the heavy metals lead and mercury promotes Th2 cytokine responses in vivo [12], and that high lead exposure in utero causes persistent elevation of IgE in the offspring [13]. Therefore, the current authors postulated that a high foetal exposure to the antioxidant trace elements (selenium, zinc, copper and manganese) might decrease the risk of wheezing and eczema in early childhood, and that high foetal exposure to lead and mercury might increase the risk of these conditions.…”

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

“…Blood lead levels were not available in this study. Miller et al (1998) compared responses of the immune system between fetal and adult exposures.…”