哮喘气道炎症与Ⅰ型及Ⅱ型T辅助细胞的演变

目的　探讨T淋巴细胞的增殖和分化在哮喘气道炎症过程中的变化。方法　选择初治未经皮质激素治疗的中重度急性加重期哮喘患者 2 0例 ,缓解期患者 15例 ,正常对照组 10名。SD大鼠 16只 ,按随机表法分为实验组和对照组 ,每组 8只 ,实验组给予卵清蛋白致敏激发。采用流式细胞分析技术检测哮喘患者及大鼠外周血分泌干扰素γ(IFN γ)的CD4 、CD8 细胞及分泌白细胞介素 4(IL 4 )的CD4 细胞的百分数。结果　 (1)哮喘急性加重期患者外周血分泌IFN γ的CD4 细胞(30 %± 10 % )和CD8 细胞 (4 2 %± 15 % )均高于缓解期患者 (分别为 2 0 %± 8% ,P <0 0 1;30 %±10 % ,P <0 0 1)和正常人 (分别为 18%± 8% ,P <0 0 1;2 4 %± 9% ,P <0 0 1) ;分泌IL 4的CD4 细胞 (4 2 %± 1 6 % )也显著高于缓解期患者 (2 0 %± 0 8% ,P <0 0 1)及正常人 (1 9%± 0 9% ,P <0 0 0 1)。缓解期患者与正常人之间上述各参数差异无显著意义。 (2 )哮喘模型大鼠外周血分泌IFN γ的CD4 细胞在激发 2h后开始升高 (5 7%± 1 6 % ) ,并在 10h时达到高峰 (9 9%± 4 4 % ) ,以后逐渐下降 ;分泌IFN γ的CD8 细胞在激发后 2h开始增高 (11 5 %± 5 1% ) ,并于 10h达到高峰 (38 7%± 6 3% ) ,以后逐渐下降 ;分泌IL 4的CD4

The evolvement of Th1/Th2 imbalance accommodates to the progress of airway inflammation in asthmatic subjects and rat model

OBJECTIVE: To observe the production of IFN-gamma and IL-4 released in peripheral T lymphocytes in asthmatic patients and rat models and to clarify the dynamic changes of proliferation and differentiation of T lymphocytes during the progress of airway inflammation. METHODS: Twenty patients with moderate to severe acute exacerbation and 15 patients with remission of asthma were included in this study. Ten normal volunteers were also enrolled as control group. T lymphocytes were obtained from their peripheral blood and the percentage of IFN-gamma(+)CD4(++), IFN-gamma + CD8(++) and IL-4(+)CD4(++) cells were determined by flow cytometric method. Asthmatic rat models were established by sensitizing and challenging by ovalbumin (OVA), and the blood samples were taken and the percentage of IFN-gamma(+)CD4(+), IFN-gamma + CD8(+) and IL-4 + CD4(+) cells were assessed 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after OVA challenge. RESULTS: (1) The percentages of IFN-gamma(+)CD4(+), IFN-gamma(+)CD8(+) and IL-4(+)CD4(+) cells in the peripheral blood were significantly higher in the patients with acute exacerbation [(30% +/- 10%), (42% +/- 15%), and (4.2% +/- 1.6%) respectively] than those in the patients with remission asthma [(20% +/- 8%), (30% +/- 10%), and (2.0% +/- 0.8%) respectively, and P < 0.001;] and those in the normal subjects [(18% +/- 8%), and (24% +/- 9%), P < 0.01, and (1.9% +/- 0.9%), P < 0.001; respectively]. But all the parameters were not different significantly between the patients with remission asthma and the normal subjects. (2) In the asthmatic rat models, the IFN-gamma(+)CD4(+) cells in peripheral blood increased 2 h after OVA challenge (5.7% +/- 1.6%), and peaked 10 h after (9.9% +/- 4.4%), and decreased afterwards. The IFN-gamma(+)CD8(+) cells in peripheral blood increased 2 h after (11.5% +/- 5.1%) OVA challenge, and peaked 10 h after (38.7% +/- 6.3%), and then decreased afterwards. The IL-4(+)CD4(+) cells increased 2 h (1.7% +/- 1.0%) after OVA challenge, and peaked 36 h after (4.0% +/- 1.6%), and then decreased. CONCLUSION: Both Th1 (IFN-gamma) and Th2 (IL-4) cytokines generated by peripheral blood mononuclear cells in asthma subjects and asthmatic rat models play a role in the development of airway inflammation in bronchial asthma dynamically. Th1 cytokines dominate at the early stage of airway inflammation, whereas Th2 cytokines achieves the major effects at later stage of the inflammation. It suggests that using different strategy in treatment of asthmatics in early stage and late stage may be necessary to control asthma.