Autoimmune thyroiditis is a multifactorial disease in which genetic predisposition combines with environmental factors to induce disease. In humans, the thyroid can be compromised by diet, drugs, and other synthetic chemicals. Excess iodine may be partially responsible for the increasing prevalence of autoimmune thyroiditis. Other environmental chemicals may also be implicated, but there is little documented evidence as to which chemicals may be involved. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenyls, and polychlorinated biphenyls. Infectious agents are also known to trigger autoimmunity. In this proposal the investigators will 1) develop standard reproducible conditions for obtaining a 50% incidence of iodine-exacerbated autoimmune thyroiditis in NOD.H2h4 mice and 2) use this mouse model to study the effects of environmental chemicals in food, industrial products, or infection on development of autoimmune thyroiditis. Methylcholanthrene (MCA) will be used as an example of a polyaromatic hydrocarbon, KBr will be used as an example of a polybrominated biphenyl, and theophylline will be used as an example of a drug which can increase iodine uptake.
In Aim 3, lipopolysaccharide (LPS) will be used as a surrogate for infection to determine the role of infectious agents in autoimmune thyroiditis. The genetic predisposition of the NOD.H2h4 mouse to autoimmune thyroiditis will be used to study the potential additive effects of the above compounds on autoimmune disease. The NOD.H2h4 animals are an ideal sentinel model to examine the potential interactions of genetics and environmental agents on autoimmune disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES010285-03
Application #
6382344
Study Section
Special Emphasis Panel (ZES1-JPM-B (R))
Program Officer
Mastin, Patrick
Project Start
1999-09-30
Project End
2003-09-29
Budget Start
2001-09-30
Budget End
2003-09-29
Support Year
3
Fiscal Year
2001
Total Cost
$163,800
Indirect Cost
Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Burek, C Lynne; Talor, Monica V (2009) Environmental triggers of autoimmune thyroiditis. J Autoimmun 33:183-9
Rose, Noel R; Bonita, Raphael; Burek, C Lynne (2002) Iodine: an environmental trigger of thyroiditis. Autoimmun Rev 1:97-103