白细胞介素-12对哮喘患者Th细胞的作用

Effects of IL-12 on T helper cells of patients with asthma

目的 观察白细胞介素 12 (IL 12 )对哮喘患者辅助性T淋巴细胞 (Th)的分化和细胞因子分泌的影响 ,探讨IL 12对哮喘治疗的机制及应用。方法 从哮喘患者外周血分离出单核细胞和CD4 + T(Th)细胞 ,单核细胞被尘螨变应原刺激活化后同CD4 + T细胞分别与 1μg·L-1和 5 μg·L-1IL 12共培养 ,对照组不加IL 12。 72h后收集培养上清 ,ELISA法检测IL 4、IL 5和IFN γ的生成量。培养细胞用荧光标记的单克隆抗体染色 ,流式细胞仪 (FCM)检测细胞内特异性细胞因子。结果 与对照组相比 ,实验组IL 4、IL 5的产生量明显减少 ,IFN γ的产生量显著增加 (P <0 .0 1) ,而且这种变化趋势在 1μg·L-1、5 μg·L-1IL 12间也有统计学差异 (P <0 .0 5 )。实验组Th1/Th2向Th1方向漂移 ,Th1/Th2增加 (P<0 .0 1)。结论 IL 12可调节Th的分化方向及不同类型细胞因子的分泌 ,并在一定浓度范围内呈量效依赖性。提示IL

Objective To investigate the effects of IL-12 on differentiation and cytokine production of T helper cells and explore its pathogenesis and potential treatment on asthma. Methods The subjects were divided into two groups, receiving 1 μg·L -1and 5 μg·L -1 of IL-2, respectively. Monocytes and CD4 +T cells were isolated from peripheric blood of 10 patients with asthma. Stimulated with dust mite extract, monocytes and CD4 +T cells were co-cultured with or without addition of IL-12. After 72 hours, the 150μL supernatants were harvested. IL-4, IL-5 and IFN-γ releases were assessed by ELISA and compared with spontaneous release. The percentages of Th1 and Th2 marked by fluorescent antibody (IL-4Ab & IFN-γAb) were examined through FCM. Results After induction of IL-12, the production of IL-4 and IL-5 was reduced by CD4 +T cells, and IFN-γ release was increased compared with the control (P< 0.01). There was a significant difference in the production of cytokines of T helper cells between 1 μg·L -1 and 5 μg·L -1 groups (P<0.05), and dose-dependent characteristics were shown during a certain range of density. In contrast with the controls, the percentage of Th1/Th2 was increased. Conclusion These data indicate that IL-12 can inhibit the production of IL-4 and IL-5 by Th2 and enhance IFN-γ secretion by Th1. At the same time, IL-12 promotes Th to differentiate toward Th1 and regulates the Th1/Th2 balance. IL-12 may be a possible therapy for asthma.