Project Summary (2000-2006)

Autoimmune disorders effect upwards of 10 million Americans, and it is clear that for most of these disorders both genetic and environmental factors contribute to the development and progression of disease. Several chemicals have been shown to have estrogen-like effects, and one mechanism by which environmental toxicants might influence the appearance or severity of autoimmune diseases is by mimicking the effects of estrogen. Project investigators have shown that three chlorinated pesticides (o,p’-DDT, chlordecone, and methoxychlor) have estrogenic effects in vivo, significantly accelerating the development of autoimmune disease in lupus model mice. Investigators are extending these observations by establishing dose-response relationships, no-effect levels and body burdens on key tissues corresponding to dosage for each of the toxicants. A related objective will be to determine whether autoimmune effects can be elicited by these agents following fetal and neonatal exposure. The hypothesis that the development and progression of autoimmune disease is due to estrogen activity is also being tested in mice administered an estrogen antagonist, and a potential mechanism is being examined. In summary, three prototype environmental estrogenic chemicals (o,p’-DDT, chlordecone, and methoxychlor) are being studied to test the principle that environmental estrogens can initiate or exacerbate autoimmune disease, as well as to provide important information regarding the mechanisms through which immune function is altered by these agents.