地塞米松和伊曲康唑对螨致敏哮喘小鼠模型中烟曲霉加重的过敏性气道炎症的差异作用。
Differential effects of dexamethasone and itraconazole on Aspergillus fumigatus-exacerbated allergic airway inflammation in a murine model of mite-sensitized asthma.
机构信息
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
出版信息
Respiration. 2013;85(5):429-35. doi: 10.1159/000345861. Epub 2013 Jan 15.
BACKGROUND
Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined.
OBJECTIVES
The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation.
METHODS
Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice.
RESULTS
Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df-sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice.
CONCLUSIONS
The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma.
背景
真菌暴露与特别严重的哮喘有关。然而，抗真菌治疗对真菌加重哮喘的影响仍需确定。
目的
本研究旨在比较伊曲康唑（ITCZ）和地塞米松（Dex）对烟曲霉（Af）加重的预先存在的屋尘螨（Df）过敏原致敏的过敏性气道炎症的作用。
方法
制备四组 BALB/c 小鼠：对照组、Df 致敏加 Af 感染组（Df-Af）、Df-Af 用 Dex 治疗组（Df-Af-Dex）和 Df-Af 用 ITCZ 治疗组（Df-Af-ITCZ）。评估气道中的肺病理学和细胞因子谱。在另一组实验中，测定 Dex 对 Df 致敏小鼠肺泡巨噬细胞（AM）吞噬 Af 分生孢子的影响。
结果
Af 感染显著增加了 Df 致敏小鼠气道中的嗜酸性粒细胞和中性粒细胞水平。Dex 显著降低嗜酸性粒细胞，而 ITCZ 则显著降低 Df-Af 小鼠中的嗜酸性粒细胞和中性粒细胞。Dex 显著降低 IL-5，而 ITCZ 则显著降低气道中的 MIP-2。与对照组相比，从 Df 致敏小鼠分离的 AM 对 Af 分生孢子的吞噬活性显著降低。然而，Dex 显著改善了 Df 致敏小鼠 AM 的吞噬活性。
结论
本研究表明，Dex 和 ITCZ 以不同的方式调节 Af 加重的过敏性气道炎症；前者抑制嗜酸性粒细胞炎症，后者通过调节不同的细胞因子抑制中性粒细胞和嗜酸性粒细胞炎症。此外，Dex 增强了过敏性哮喘中 AM 的吞噬活性。因此，Dex 和 ITCZ 的联合可能对管理真菌加重的哮喘有效。
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