THYROCYTES EXPRESS INFLAMMATORY MEDIATORS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Graves' disease is a common autoimmune (inflammatory) disease. The pathogenic mechanisms underlying autoimmune disease such as Graves' disease, rheumatoid arthritis, Hashimoto's thyroiditis, etc. are largely unknown. Patients with Graves' disease are hyperthyroid (hyper) and can develop a thyroid goiter, ophthalmopathy (eye bulging) and or dermopathy (skin swelling). Our understanding of Graves' disease remains superficial and current treatment is symptom oriented. The organs and tissues named above are infiltrated by lymphocytes (immune cells). We believe that antibodies and other factors (IL-16) present in the blood stream of patients with autoimmune disease are important mediators of this inflammatory process. We are studying the factors responsible for this inflammatory response characteristic of Graves' tissues (Thyroid, Orbit, Skin), rheumatoid arthritis tissues (synovium). We will extract antibodies from the blood samples donated by the patients and use them in cell culture experiments. Primary thyrocyte and fibroblast cell cultures will be developed from thyroid or connective tissue salvaged from surgical waste. These experiments will 1) investigate the pathogenesis of Grave's inflammation and 2) identify potential therapeutic targets for interrupting the processes which leads to the development of Graves' and potentially other autoimmune diseases. Some patients with Graves' disease have elevated levels of the cytokine IL-16 in their blood. We will measure and follow (for 48 months) IL-16 levels in the blood of patients with Graves' disease and attempt to correlate these levels with the clinical severity and progression (for 48 months) of the Graves' disease. IL-16 levels will also be measured in normal control subjects. Another purpose of this study is to examine the differences between fibroblasts from the orbit (space around the eye) and fibroblasts from skin obtained from the leg, arm and other parts of the body. We have found that fibroblasts from these different body areas exhibit phenotypes that diverge. Those fibroblasts from the orbit and joint space appear particularly susceptible to inflammatory reactions. We hypothesize that it is in this susceptibility that underlies the inflammation of Graves' disease and rheumatoid arthritis, respectively.