Vine et al., (2000)
examined the relationship between exposure to environmental toxicants (e.g. organochlorine pesticides, volatile organic compounds, and metals) found in a Superfund site in Aberdeen, North Carolina, on DNA damage and immune function of inhabitants living near the site. Of the immune markers analyzed in the study population of over 200 subjects [these included cell counts, levels of immunoglobulins (Igs), skin prick test, and mitogen stimulation assays] only mitogen proliferation was signficantly lower in subjects who lived near the site. There was no significant difference in cell counts (6 analyzed) or Igs (4 analyzed). The authors acknowledged that these markers were relatively broad indicators of immune function and proposed more specific immune assays (cytokine analysis). However, they did not carry it out because of the cost constraints. Since then, numerous studies have used immune markers that include cytokine profiles, to evaluate the effect of environmental toxicants such as volatile organic compounds (VOCs), pesticides, polychlorinated biphenyls (PCBs), and metals on children's immunity ().
Cytokine and other immunological biomarkers used to evaluate potential immunotoxic effects of environmental exposures
In a study of the effects of VOCs on newborn immune development (n=85), VOC exposure was ascertained with passive sampling of the maternal indoor environment and immune function was measured by detection of intracellular IFN-γ and IL-4 cytokine production (Lehmann et al., 2002
). The authors report that exposure to naphthalene was associated with increased IL-4 cytokine production and decreased IFN -γ production was associated with trichloroethylene In other studies, no association was found between children's exposures to mercury (Bilhra et al., 2003) and IL-10 and TNF-a levels, however increased levels of GM-CSF was associated with children's exposure to arsenic (Soto-Pena et al., 2006
). In a large longitudinal birth cohort study (N=540) from Czech Republic (Sram, 2001
), lymphocyte immunophenotyping was conducted in two groups of mothers and their newborns that lived either in clean air area (Prachatice) or in the area polluted from power plants and coal home heating (Teplice) (Hertz-Picciotto et al., 2006). A significantly lower percent of T lymphocytes and the %CD4 of the total T-cells were observed in both maternal and cord blood in polluted area with a more pronounced decline during winter months. Additionally, after three years of follow up, children born in Teplice experienced a significantly higher rate of otitis media, respiratory and gastrointestinal infections, and pneumonia that indicates air pollution affected their susceptibility. Karmaus et al. (2005)
reported immune function biomarkers (cell counts and antibody production) in children exposed to lead and organochlorine compounds in a cross-sectional study. Their findings indicate that lead is associated with increased IgE production, corroborating a prior report by Lutz et al. (1999)
. However, cytokines profiles were not evaluated. Since IgE production is a direct result of IL-4 (and IL-13) production, it would be important to examine cytokine levels in children exposed to lead in future studies. In CHAMACOS, a longitudinal birth cohort in Salinas Valley, California (Eskenazi et al, 2003
), the relations between early childhood exposures to an agricultural environment and Th1 and Th2 cytokines were investigated in 24 month old children (n=239) (Duramad et al, 2006
). Exclusive breastfeeding at one month and pet ownership were associated with increased Th1 whereas increased Th2 was associated with maternal agricultural work and the presence of gas stove in the home. Bilhra et al., (2003) found that newborns exposed to organochlorines in utero
had significantly decreased production of TNF-a, an important proinflammatory cytokine, suggesting that these children may be more susceptible to infections. These data indicate further that early exposures to environmental toxicants can directly impact the development and function of children's immunity.