Cytokine gene expression in autoimmune thyroiditis in BioBreeding/Worcester rats

The intrathyroidal cytokine gene expression in human autoimmune thyroid dis ease is difficult to interpret because surgical specimens mostly reflect th e autoimmune disease at a late stage. Because it is not possible to investi gate early stages of thyroiditis in humans, the Bio Breeding/Worcester (BB/ W) rat was used as a model. To characterize the lymphocytic thyroiditis (LT ) of BB/W rats further and to evaluate early increases of cytokine gene exp ression in LT, we investigated the interleukin (IL)-2, -4, -6, -10, -12p40, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) g ene expression in the thyroids, spleens, and livers of BB/W rats with and w ithout histological evidence for thyroiditis. The gene expression of these cytokines was determined by Genescan (PE Applied Biosystems, Foster City, C A) fragment analysis using reverse polymerase chain reaction (RT-PCR). Seru m thyroglobulin (Tg) antibody concentrations were measured and the extent o f lymphocytic infiltration of one thyroid lobe was histologically graded. C ytokine gene expression in rats with and without LT was compared in three g roups of rats: 55-day-old rats after 24 days of iodine administration, 75-d ay-old rats after 45 days of iodine administration, and 101-day-old rats. I n the thyroids of the BB/W rats no expression of IL-4 or IL-10 was detectab le. The number of rats with detectable TNF-alpha, IFN-gamma, IL-2, IL-12p40 gene expression was significantly higher in rats with LT. Rats with LT had significantly higher IL-12p40 mRNA levels. There were no significant diffe rences in the IL-6 gene expression between rats with and without LT. A corr elation between the level of lymphocytic infiltration and the TNF-alpha (r = 0.56, p < 0.0065) and TG antibody concentration (r = 0.62, p < 0.0065) wa s found. Therefore, the early cytokine gene expression in the BB/W rat is c haracterized by Th1-related cytokines like IL-2 and IFN-gamma. Whether the detected IL-12p40 (10 rats) and IFN-gamma (5 rats) gene expression in anima ls without LT is an early indicator for the development of LT remains to be determined.