Developmental Exposure to Lead Causes Persistent Immunotoxicity in Fischer 344 Rats

• Published in: Toxicological sciences 1998-04, Vol.42 (2), p.129-135
• Main Authors: Miller, T. E., Golemboski, K. A., Ha, R. S., Bunn, T., Sanders, F. S., Dietert, R. R.
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation - drug effects; Biological and medical sciences; Body Weight; Embryology: invertebrates and vertebrates. Teratology; Embryonic and Fetal Development - drug effects; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Hypersensitivity, Delayed; Immunity, Cellular - drug effects; Immunoglobulin E - blood; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lead - blood; Lead - toxicity; Leukocyte Count - drug effects; Nitric Oxide - biosynthesis; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred F344; Superoxides - metabolism; Teratology. Teratogens; Tibia - chemistry; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/42.2.129

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.