Institute of Integrated Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Ann Allergy Asthma Immunol. 2009 Dec;103(6):525-34. doi: 10.1016/S1081-1206(10)60270-0.
Glucocorticoids play an important role in modulating allergic inflammation and immune response. However, little is known about the role of endogenous glucocorticoids in airway allergic disease.
To investigate the effects of endogenous glucocorticoids on regulating allergic inflammation and T(H)1/T(H)2 balance in an airway allergic murine model.
An ovalbumin-sensitized murine model was established by intraperitoneal injection sensitization and intranasal challenge with ovalbumin. Glucocorticoid release was inhibited by administration of metyrapone, and the peripheral glucocorticoid receptors were blocked by administration of RU486. The numbers of eosinophils in the lung, peripheral blood, and bone marrow were quantified. The changes in T(H)2/T(H)1 cells were investigated by flow cytometry, and their cytokines were tested by enzyme-linked immunosorbent assay, including interleukin 4, interleukin 5, and interferon gamma, in the supernatant of the spleen cell culture.
Inhibition of endogenous glucocorticoids caused more sneezing and further increased eosinophil counts in the peripheral blood and bone marrow of the sensitized mice. However, by inhibition of endogenous glucocorticoids, the interferon gamma levels were upregulated, the interleukin 4 and 5 levels were down-regulated, and the ratio of T(H)2/T(H)1 cells decreased significantly, indicating a shift to a T(H)1-predominant immune response in sensitized mice.
Our findings suggest that endogenous glucocorticoids play an important role in abating allergic inflammatory reaction and modulating the T(H)1/T(H)2 balance in an airway allergic murine model. Inhibition of endogenous glucocorticoids resulted in a shift to T(H)1 predominance, but that did not attenuate the severity of the allergic inflammatory reaction.
糖皮质激素在调节过敏炎症和免疫反应方面发挥着重要作用。然而，人们对内源性糖皮质激素在气道变应性疾病中的作用知之甚少。
研究内源性糖皮质激素在调节气道变应性小鼠模型中的过敏炎症和 T(H)1/T(H)2 平衡中的作用。
通过腹腔注射致敏和卵清蛋白鼻内激发建立卵清蛋白致敏的小鼠模型。用美替拉酮抑制糖皮质激素释放，用 RU486 阻断外周糖皮质激素受体。定量检测肺、外周血和骨髓中的嗜酸性粒细胞数。通过流式细胞术检测 T(H)2/T(H)1 细胞的变化，通过酶联免疫吸附试验检测脾细胞培养上清液中细胞因子的变化，包括白细胞介素 4、白细胞介素 5 和干扰素 γ。
抑制内源性糖皮质激素可导致致敏小鼠打喷嚏次数增多，外周血和骨髓中嗜酸性粒细胞计数进一步增加。然而，通过抑制内源性糖皮质激素，干扰素 γ 水平上调，白细胞介素 4 和白细胞介素 5 水平下调，T(H)2/T(H)1 细胞比值显著降低，表明致敏小鼠向 T(H)1 优势免疫反应转变。
我们的研究结果表明，内源性糖皮质激素在减轻气道变应性小鼠模型中的过敏炎症反应和调节 T(H)1/T(H)2 平衡中发挥着重要作用。抑制内源性糖皮质激素导致 T(H)1 优势，但并未减轻过敏炎症反应的严重程度。
