Blüher M, Krohn K, Wallaschofski H, Braverman L E, Paschke R
III. Medical Department, Faculty of Medicine, University of Leipzig, Germany.
Thyroid. 1999 Oct;9(10):1049-55. doi: 10.1089/thy.1999.9.1049.
The intrathyroidal cytokine gene expression in human autoimmune thyroid disease is difficult to interpret because surgical specimens mostly reflect the autoimmune disease at a late stage. Because it is not possible to investigate 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 expression in LT, we investigated the interleukin (IL)-2, -4, -6, -10, -12p40, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) gene expression in the thyroids, spleens, and livers of BB/W rats with and without histological evidence for thyroiditis. The gene expression of these cytokines was determined by Genescan (PE Applied Biosystems, Foster City, CA) fragment analysis using reverse polymerase chain reaction (RT-PCR). Serum thyroglobulin (Tg) antibody concentrations were measured and the extent of lymphocytic infiltration of one thyroid lobe was histologically graded. Cytokine gene expression in rats with and without LT was compared in three groups of rats: 55-day-old rats after 24 days of iodine administration, 75-day-old rats after 45 days of iodine administration, and 101-day-old rats. In the thyroids of the BB/W rats no expression of IL-4 or IL-10 was detectable. 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 differences in the IL-6 gene expression between rats with and without LT. A correlation 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) was found. Therefore, the early cytokine gene expression in the BB/W rat is characterized 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 animals without LT is an early indicator for the development of LT remains to be determined.
人类自身免疫性甲状腺疾病中甲状腺内细胞因子基因表达难以解读，因为手术标本大多反映的是自身免疫性疾病的晚期阶段。由于无法在人类中研究甲状腺炎的早期阶段，因此将生物繁殖/伍斯特（BB/W）大鼠用作模型。为了进一步表征BB/W大鼠的淋巴细胞性甲状腺炎（LT）并评估LT中细胞因子基因表达的早期增加情况，我们研究了有或无甲状腺炎组织学证据的BB/W大鼠的甲状腺、脾脏和肝脏中白细胞介素（IL）-2、-4、-6、-10、-12p40、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）基因的表达。这些细胞因子的基因表达通过使用逆转录聚合酶链反应（RT-PCR）的基因扫描（PE应用生物系统公司，加利福尼亚州福斯特城）片段分析来确定。测量血清甲状腺球蛋白（Tg）抗体浓度，并对一个甲状腺叶的淋巴细胞浸润程度进行组织学分级。在三组大鼠中比较有或无LT的大鼠的细胞因子基因表达：给予碘24天后的55日龄大鼠、给予碘45天后的75日龄大鼠和101日龄大鼠。在BB/W大鼠的甲状腺中未检测到IL-4或IL-10的表达。有LT的大鼠中可检测到TNF-α、IFN-γ、IL-2、IL-12p40基因表达的大鼠数量显著更高。有LT的大鼠的IL-12p40 mRNA水平显著更高。有或无LT的大鼠之间IL-6基因表达无显著差异。发现淋巴细胞浸润程度与TNF-α（r = 0.56，p < 0.0065）和TG抗体浓度（r = 0.62，p < 0.0065）之间存在相关性。因此，BB/W大鼠的早期细胞因子基因表达以IL-2和IFN-γ等Th1相关细胞因子为特征。在无LT的动物中检测到的IL-12p40（10只大鼠）和IFN-γ（5只大鼠）基因表达是否是LT发展的早期指标仍有待确定。
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