Infantile autism (IA) is a neurodevelopmental syndrome found in 1-5 of every 10,000 children. The cause of IA is unknown; however, exposure to mercury is thought to contribute to this syndrome. More specifically, childrens vaccines containing mercuric compounds such as Thimerosal (TH) have been suggested to increase risk for acquiring neurodevelopmental problems such as autism. Pathophysiological links to autism include effects such as hyperserotoninemia, decreased T-cell proliferative function and activation, increased soluble IL-2 levels in serum, decreased CD8+ cells, decreased NK cells, development of anti-brain autoantibodies, decreased cerebellum volume and Purkinje cell number, and increased brain size. TH contains ethylmercury and the most commonly reported effects include contact hypersensitivity, allergic contact dermatitis, and altered T-cell responses. As several of the reported pathophysiologies are related to altered immunity we assessed the effects of TH on immune function. B6C3F1 mice were injected i.p. with TH (0, 20, 100, or 200 g/kg) at 7, 10, and 12 days of age. A suite of immune parameters including secondary immune organ weights and cellularity, T- and B-cell proliferation, NK cell function, and T-cell immunophenotyping were assessed along with developmental markers such as eye opening, ear un-folding, body weight and length, and brain weight at 8 weeks of age. Body weight was decreased while brain weight was increased following treatment with 20 g/kg TH. NK cell function was increased after exposure to 200 ug/kg TH. Thymus weight and cellularity were not altered; however, splenic cellularity was increased by the 100 and 200 g/kg treatments. Splenic B220 cells were increased by the 100 and 200 g/kg treatments while CD4+/CD8+ and CD4+/CD8- cells were in-creased after the 200 g/kg exposure. This study identifies that postnatal exposure to TH can modulate the developing murine immune system.
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland