Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats

T. E. Miller, K. A. Golemboski, R. S. Ha, T. Bunn, F. S. Sanders, R. R. Dietert

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


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-α 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-γ 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.

Original languageEnglish
Pages (from-to)129-135
Number of pages7
JournalToxicological Sciences
Issue number2
StatePublished - Apr 1998

Bibliographical note

Funding Information:
The authors thank Suping Chen, Valerie Highfill, Christina Kim, and Kevin Fitch for their assistance with these experiments and Diane Colf for her administrative support. Additionally, the helpful discussions of Dr. Judy Ze-likoff are much appreciated. This publication was made possible by Grant ES05950 from the National Institute of Environmental Health Sciences, NIH, with funding provided by EPA.

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats'. Together they form a unique fingerprint.

Cite this