The proposed study addresses the impact of environmental lead on the developing immune system of young children. In animal model systems, lead levels far below those necessary for overt toxicity are found to be immunosuppressive. It is difficult to extrapolate these data to human systems. A study population of urban children (9 months to 6 years of age) with blood levels greater than 10 micrograms/1OO ml has been identified in the Springfield-Greene County area of Missouri through participation in local WIC (Women, Infants, and Children) and Lead Poisoning Prevention programs. This pool of children, with appropriately matched controls from the same programs, have offered an ideal opportunity to begin an assessment of possible correlations between blood lead concentrations and various immune system parameters. Preliminary studies have resulted in the selection of a number of specific assays proposed to assess possible effects of lead on cell numbers (counts of WBC types, including classes and subclasses of lymphocytes); effects on B cell function (serum Ig concentrations including IgE; cell surface class II density; cell surface density of the activation antigens CD71 (transferrin Rc) and B7]; effects on T cell function (proliferative response to IL-2; cell surface density of the activation antigens CD25 (IL-2 Rc), CD71, and CD28); and effects on concerted immune responses (specific antibody titers to vaccines; proliferative responses to antigens; release of soluble cytokine receptors (CD25 and CD27); frequencies of infections and allergies). Preliminary data have also allowed a determination of appropriate sample size and generation of essential control data for these selected parameters.
Specific aims are as follow: 1. Gather data on screening assays to reach a sample size of 30-35 children per control and experimental group, age 9 months to 6 years of age. 2. Perform screening assays to determine which component(s) of the immune system are sensitive to lead exposure. 3. Conduct a longitudinal study of selected children, with 12 and 24 month follow-up samples. 4. Conclude with exhaustive statistical analysis of data. The study will provide invaluable information on the effects of an environmental toxin on the immune system in a population at great risk for exposure. In addition, the longitudinal study will provide information on the effects of chronic lead exposure on the developing immune system. In the process, knowledge of normal immune function in young children will be increased.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Toxicology Subcommittee 2 (TOX)
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University of Missouri-Rolla
Other Basic Sciences
Schools of Arts and Sciences
United States
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Lutz, Paula M; Kelty, Elizabeth A; Brown, Tina D et al. (2012) Environmental cigarette smoke exposure modulates IgE levels of Pb-exposed children. Toxicology 291:43-50
Ercal, N; Neal, R; Treeratphan, P et al. (2000) A role for oxidative stress in suppressing serum immunoglobulin levels in lead-exposed Fisher 344 rats. Arch Environ Contam Toxicol 39:251-6
Lutz, P M; Wilson, T J; Ireland, J et al. (1999) Elevated immunoglobulin E (IgE) levels in children with exposure to environmental lead. Toxicology 134:63-78
Ercal, N; Treeratphan, P; Lutz, P et al. (1996) N-actylcysteine protects Chinese hamster ovary (CHO) cells from lead-induced oxidative stress. Toxicology 108:57-64