Th1/Th2在支气管哮喘大鼠气道炎症过程中的变化

目的 通过观察支气管哮喘(简称哮喘)气道炎症模型大鼠外周血T淋巴细胞分泌γ干扰素(IFN-γ)及白细胞介素4(IL-4)的变化,探讨INF-γ及IL-4在哮喘气道炎症过程中的作用,同时观察地塞米松对IFN-γ及IL-4的影响。方法 24只SD大鼠按随机数字表法分为实验组(A组,16只)和对照组(B组,8只),根据实验需要又将实验组16只大鼠分为卵清蛋白致敏激发组(A1组)、激发前激素预处理组(A2组),每组8只。建立哮喘气道炎症大鼠模型采用流式细胞胞内染色技术,测定A1组、A2组[给予地塞米松腹腔注射(10 mg/kg)]和B组大鼠外周血分泌IFN-γ的CD4 、分泌IL-4的CD4 和分泌IFN-γ的CD4 细胞在激发后不同时间点的数值。结果 A1组大鼠外周血中IFN-γ 的CD4 细胞、IFN-γ 的CD4 细胞及IL-4 的CD4 细胞在雾化2 h时分别为(5.7±1.6)％、(11.5±5.1)％、(1.66±0.95)％,A2组分别为(2.6±1.3)％、(3.9±1.5)％、(0.77±0.37)％,B组分别为(1.8±0.7)％、(6.1±1_8)％、(0.65±0.12)％。A1组与A2组比较及A1组与B组比较,差异有显著性(P均<0.05)。A1组大鼠外周血中IFN-γ 的CD4 细胞及IFN-γ 的CD8 细胞在雾化10 h时出现高峰,分别为(9.9±4.4)％、(38.7±6.3)％、A2组分别为(4.9±1.7)％、(15.7±8.7)％,B组分别为(1.5±0.5)％、(6.4±1.5)％,A1组

The evolvement of Th1/Th2 imbalance in the process of airway inflammation in a rat asthmatic model

OBJECTIVE: T lymphocytes play an important role in the development of asthmatic airway inflammation. By observing the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) released by peripheral T lymphocytes in asthmatic rat models, this study was designed to clarify the changes of T lymphocytes during the course of airway inflammation. The influence of dexamethasone pre-treatment on the production of IFN-gamma and IL-4 by T lymphocytes was also investigated in the study. METHODS: Twenty-four rats were divided into the study group (group A) and the control group (group B). In the study group, rats were subdivided into two groups with 8 rats in each group. one group (group A(2)) received pre-treatment with intraperitoneal injection with dexamethasone (10 mg/kg), and another group (group A(1)) did not receive dexamethasone pre-treatment, The control group was matched with the study group with regard to both age and weight. Rats were sensitized and challenged by ovalbumin (OVA), and blood samples were obtained and the percentage of IFN-gamma(+)CD(4)(+), IFN-gamma(+)CD(8)(+) and IL-4(+)CD(4)(+) cells were assessed by intracellular cytokine staining and flow cytometric analysis at 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 36 h, 48 h, 72 h, 6 d, 9 d, 12 d, and 15 d after OVA challenge. RESULTS: In group A(1), the peripheral IFN-gamma(+)CD(4)(+) cells, IFN-gamma(+)CD(8)(+) cells, and IL-4 CD(4)(+) cells increased 2 h after OVA challenge [(5.7 +/- 1.6)%, [(11.5 +/- 5.1)%, (1.66 +/- 0.95)%] compared with group A(2) [(2. 6 +/- 1.3)%, (6.1 +/- 1.8)%, (0.77 +/- 0.37)%, P < 0.05 respectively] and group B [(1.8 +/- 0.7)%, (3.9 +/- 1.5)%, (0.65 +/- 0.12)%, P < 0.05 respectively]. The peripheral IFN-gamma(+)CD(4)(+) cells and IFN-gamma(+) CD(8)(+) cells in group A(1) reached their maximal level at 10 h [(9.9 +/- 4.4)%, (38.7 +/- 6.3)%] compared with group A(2) [(4.9 +/- 1.7)%, (15.7 +/- 8.7)%, P < 0.05 respectively and group B [(1.5 +/- 0.5)%, (6.4 +/- 1.5)%, P < 0.05 respectively], and then decreased afterward. The IL-4(+) CD(4)(+) cells in group A(1) at 10 h after challenge was (2.16 +/- 0.75)%. There was no statistical difference compared with group A(2) [(1.39 +/- 0.77)%, P > 0.05], but it was higher than group B [(0.68 +/- 0.15)%, P < 0.05]. The highest level of IL-4(+) CD(4)(+) cells of group A(1) was observed at 36 h [(4.0 +/- 1.6)%], and there was a statistical difference compared with group A(2) [(1.5 +/- 1.0)%, P < 0.05] and group B [(0.7 +/- 0.3)%, P < 0.05]. CONCLUSIONS: Both IFN-gamma and IL-4 generated by peripheral blood T cells in the rat asthmatic models played a role in the development of airway inflammation. INF-gamma dominated at early stage of the airway inflammation, whereas IL-4 took the major effect at the late stage of inflammation. The production of IFN-gamma and IL-4 by T lymphocytes in the asthmatic model was inhibited significantly by dexamethasone.