血清IL-10和IL-12在自身免疫性甲状腺疾病中的表达特征

目的：研究自身免疫性甲状腺疾病中血清白细胞介素－10（IL－10）和白细胞介素－12（IL－12）的表达特征及其在免疫反应发生中的作用和机制。方法：对38例Graves病（GD）患者（18例未治疗的初诊患者，为GDa组；20例抗甲亢药物治疗的患者，为GDb组）、24例慢性淋巴细胞性甲状腺炎（HD）患者及22例正常者（对照组）检测了血清中IL－10，IL－12的表达水平及甲状腺功能的变化。IL－10和IL－12采用酶联免疫法（ELISA）测定。血清游离T3（FT3），游离T4（FT4）和促甲状腺激素（TSH）测定用化学发光免疫分析法。抗甲状腺球蛋白抗体（TgAb)和抗甲状腺微粒体抗体（TmAb)用放射免疫法。结果：GDa组的IL－10、IL－12均高于对照组（P＜0．05，P＜0．01），但以IL－12的增高占优势，IL－12／IL－10比值增高（P＜0．05）。GDb组的IL－12水平和IL－12／IL－10比值较GDa组显著降低（P＜0．05，P＜0．01），与对照组比较无显著差异。IL－10水平较GDa组有上升趋势但无统计学意义，但高于对照组（P＜0．01），HD患者IL－12水平和IL－12／IL－10比值均较对照组增高（P＜0．01，P＜0．01），较GDb组也显著增高（P＜0．05，P＜0．01），IL－10水平与对照组比较无显著差异，但显著低于GDb组（P＜0．05）。结论：GD患者，在甲状腺功能亢进状态时，由Thl细胞产生的IL－12水平和低表Th2细胞活力的IL－10水平均明显增高，提示Th1和Th2的表达均增高，细胞免疫和体液免疫均参入了甲亢的自身免疫反应过程。在HD患者也有IL－12水平的显著增高，表明了Th1细胞因子所介导的细胞免疫在HD的病理反应中起主导作用。在GD和HD患者，均表现有IL－12／IL－10比值的变化，提示Th1/Th2间的平衡紊乱可能对介导甲状腺自身免疫炎症反应的产生起关键作用。

Expression of Serum IL - 12 and IL - 10 in Autoimmune Thyroid Disease

Objective: To study the expression of serum interleukin- 12 (IL-12) and interleukin - 10 (IL-10) in autoimmune thyroid disease. Methods: Serum IL- 12, IL-10 and thyroid hormone were determined in 38 patients with Graves' disease (GD) (18 cases untreated, GDa group; 20 cases treated with anti - hyperthyroid drugs, GDb group) , 24 patients with Hashimoto's thyroiditis (HD) and 22 control cases. The IL-12 and IL-10 levels were determined by ELISA; the levels of free T3 (FT3), free T4 (FT4) and thyrotropin hormone (TSH) were examined with radioimmunoassay. Results: In GDa group, both IL- 10 and IL-12 levels increased compared with control group (P<0.05 and P<0.01), IL- 12/IL- 10 ratio also increased (P<0.05). In GDb group, IL-12 and IL- 12/IL- 10 decreased significantly compared with GDa group (P <0.05 and P<0.01), and reversed to control level, the level of IL-10 significantly increased compared with control (P< 0.01). In HD subjects, both IL - 12 and IL - 12 / IL - 10 increased significantly compared with control (P < 0. 01 and P < 0.01), and also increased compared to GDb group (P<0.05 and P<0.01), the level of IL-10 was not changed significantly compared with control group but decreased compared with GDb group (P<0.05). Conclusion: GD patients, in the hyperthyroid state, IL-12 produced from Thl cells and IL - 10 from Th2 cells increased, suggesting that both of TH1 mediated cell immunity and Th2 mediated humoral immunity take part in pathogenesis of GD. Whereas in HD patients, the increase of IL -12 level show a systemic shift of cytokine production toward the Thl cytokine response. The variation in ratios of IL - 12 to IL - 10 in GD and HD patients suggest the key role of changes in Thl/Th2 cytokine balance in the pathogenesis of autoimmune thyroid disease.