FK506对实验性过敏性结膜炎细胞因子表达的影响

目的：探讨FK506对过敏性结膜炎动物模型局部Th1/Th2免疫平衡的调控作用机制。方法：选取SPF级Balb/c鼠80只,腹腔注射卵白蛋白磷酸缓冲液（PBS）诱导动物模型。实验动物分设4组：阳性对照组（模型组）20只、地塞米松滴眼组（DM组）20只、FK506滴眼组（FK506组）20只和阴性对照组（正常组）20只。动物模型诱导成功后第15d开始,地塞米松组和FK506组分别给予局部1g/L地塞米松滴眼液和1g/LFK506滴眼液,4次/d。大鼠1眼标本用于组织学检测,对侧眼标本用于细胞因子检测。结果：模型组嗜酸性粒细胞及CD4＋淋巴细胞强阳性率均为85%。DM组CD4＋淋巴细胞强阳性率为50%,嗜酸性粒细胞强阳性率为40%。FK506组CD4＋淋巴细胞强阳性率为30%,嗜酸性粒细胞强阳性率为40%。模型组IL-4,IL-6,IL-10,IL-2,IL-12和IFN-γ水平明显高于正常组（F=11.278,P=0.000）,而且IL-4/IFN-γ,IL-6/IFN-γ,IL-10/IFN-γ比值也明显高于正常组（F=8.965,P=0.000）。DM组IL-4,IL-6,IL-10水平较模型组明显降低（F=13.972,P=0.000）,IL-12水平上升（F=6.408,P=0.002）,IL-2和IFN-γ水平无明显变化（F=1.824,P=0.306）。FK506组IL-4,IL-6和IL-10水平较模型组明显降低（F=10.582,P=0.000）,IL-12水平上升（F=9.643,P=0.001）,IL-2和IFN-γ水平无明显变化（F=2.529,P=0.407）。FK506组IL-4,IL-6和IL-10水平较DM组明显降低（F=11.281,P=0.000）,IL-12水平上升（F=8.634,P=0.003）,IL-2和IFN-γ水平无明显变化（F=0.756,P=0.305）。结论：FK506对嗜酸性粒细胞及CD4＋淋巴细胞的抑制作用明显强于地塞米松。FK506可促使过敏性结膜炎小鼠局部Th1/Th2淋巴细胞失衡向Th2方向漂移,而且其效果优于地塞米松。

Influence of FK506 on the cytokine expression in experimental allergic conjunctivitis

AIM:To investigate the immunomodulatory mechanism of FK506 on the local Th1/Th2 balance in mice model of experimental allergic conjunctivitis. METHODS: Experimental allergic conjunctivitis model was established through peritoneal injection of phosphate buffered saline(PBS) in SPF level Balb/c mice. In all, 80 mice were equally divided into 4 groups: model group, Dexamethasone (DM) group, FK506 group, and normal group. Fifteen days after the introduction of experimental allergic conjunctivitis, DM group and FK506 group mice were treated by 1g/L Dexamson eyedrops and FK506 eyedrops respectively, four times a day. Samples from one eye of the mice were used for histological study, while samples from the other eye were used for detection of interleukins. RESULTS: The strong positive rate (SPR) of eosinophilic granulocyte and CD4+ lymphocyte were both 85% in model group. SPR of eosinophilic granulocyte was 50%,and CD4+ lymphocyte was 40% in DM group. SPR of eosinophilic granulocyte was 30%,and CD4+ lymphocyte was 40% in FK506 group. The level of IL-4,IL-6,IL-10,IL-2,IL-12,IFN-γ were significantly higher in model group compared with normal group (F=11.278,P=0.000),while IL-4/IFN-γ,IL-6/IFN-γ, IL-10/IFN-γ were also significantly higher than normal group (F=8.965,P=0.000). The level of IL-4,IL-6, IL-10 was significantly lower in DM group compared with model group(F=13.972, P=0.000), the level of IL-12 significantly higher(F=6.408, P=0.002), while the level of IL-2 and IFN-γ showed no significant change(F=1.824, P=0.306). The level of IL-4,IL-6,IL-10 was significantly decreased in FK506 group compared with model group(F=10.582, P=0.000), the level of IL-12 was significantly increased(F=9.643, P=0.001),while the level of IL-2 and IFN-γ showed no significant change(F=2.529, P=0.407). The level of IL-4,IL-6,IL-10 was significantly reduced in FK506 group compared with DM group(F=11.281, P=0.000), the level of IL-12 was significantly increased(F=8.634, P=0.003),while the level of IL-2 and IFN-γ showed no significant change(F=0.756, P=0.305). CONCLUSION: The suppressive effect of FK506 on eosinophilic granulocyte and CD4+ lymphocyte was evidently stronger than that of Dexamethasone. FK506 can shift the local Th1/Th2 balance of experimental allergic conjunctivitis toward Th2 direction with better effect than that of Dexamethasone.