Infantile autism (IA) is a neurodevelopmental syndrome with 1-5 cases found in every 10,000 children. The spectrum of autism disorders includes a range of impaired communication and language development. Also reported are diverse immunological effects including decreased T-cell proliferative function and activation, increased serum IL-2 levels, decreased CD8+ cells, decreased NK cell function, and development of anti-neural autoantibodies. Several studies indicate that the etiology of IA is multi-factorial and includes exposure to environmental chemicals. In particular, Thimerosal, an adjuvant in vaccines that contains ethyl mercury, has been implicated in IA. This association has been criticized due to a lack of supportive experimental dose-response data. Consequently, this project was designed to compare dose-responsive immunological effects between Thimerosal and methyl mercury, a known immunotoxicant. In this phase of the study, B6C3F1 pups were exposed to MeHg (10 or 50 ug/kg) and two different exposure regimes were examined during postnatal development. Pups were exposed either on postnatal days (PND) 7, 10, and 12 or weekly on PND 7, 14, and 21. On PND 22, T-cell proliferation and the IgM plaque forming cell response were enhanced after exposure on PND 7, 14, and 21, but not affected after exposure on PND 7, 10, and 12. Weekly exposure to 50 ug MeHg/kg prior to weaning resulted in selective increases in CD8+ thymic T cells, whereas 10 ug MeHg/kg exposure on PND 7, 10, and 12 increased splenic CD4+ T-cell subpopulations. The exposure regime utilized during developmental periods must be considered when assessing mercury exposure, as this affects responses in immune parameters. This understanding may be useful when evaluating vulnerable periods of mercury exposure in children. Future studies will compare effects of Thimerosal with MeHg, and include assessment of cytokine levels, autoantibody production, serotonin levels and cognitive function.
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah