BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Wanxing Eugene Ho; Yong-Jiang Xu; Fengguo Xu; Chang Cheng; Hong Yong Peh; Steven R Tannenbaum; W S Fred Wong; Choon Nam Ong Journal: Am J Respir Cell Mol Biol Date: 2012-11-09 Impact factor: 6.914
Authors: Adrian M Stankiewicz; Joanna Goscik; Alicja Majewska; Artur H Swiergiel; Grzegorz R Juszczak Journal: PLoS One Date: 2015-11-10 Impact factor: 3.240