Department of Allergy and Immunology, Gunma Children's Medical Center, Shibukawa, Japan.
Int Arch Allergy Immunol. 2013;161 Suppl 2:129-37. doi: 10.1159/000350427. Epub 2013 May 29.
Respiratory syncytial virus (RSV) infection is associated with both the development and exacerbation of bronchial asthma. We examined eosinophil infiltration and the cytokine profiles of both airway and peripheral blood in antigen-sensitized mice infected with RSV to investigate the pathogenesis of exacerbations of asthma due to RSV infection.
Ovalbumin (OVA)-sensitized mice were challenged by OVA inhalation 3 times and then infected with RSV [10(5) TCID50 (50% of tissue culture infectious dose)/25 g body weight] or mock infection immediately after the last challenge. Animals from each group, namely, the control (PBS instead of OVA inhalation plus mock infection), RSV (PBS plus RSV), OVA (OVA plus mock) and OVA/RSV (OVA plus RSV) were analyzed. Analysis included evaluation of airway responsiveness to methacholine, pathological findings in the airway by hematoxylin and eosin (HE) and Luna staining, bronchoalveolar fluid (BALF) and peripheral leukocytes counts, and concentrations of multiple cytokines/chemokines in both BALF and serum.
Airway responsiveness was significantly enhanced in the OVA and OVA/RSV groups compared with the control group. Levels of tissue and BALF eosinophils were higher in the OVA and OVA/RSV groups than in the RSV or control group. Significantly higher levels of macrophage inflammatory protein (MIP)-1α in BALF were observed in the OVA/RSV group compared with the 3 other groups. Production of serum IL-17 was also significantly elevated in the OVA/RSV group compared with the control or OVA group.
These findings suggest that MIP-1α and IL-17 may play important roles in acute exacerbation of asthma induced by RSV in an animal model.
呼吸道合胞病毒(RSV)感染与支气管哮喘的发生和恶化都有关联。我们研究了 RSV 感染致敏小鼠的气道和外周血中的嗜酸性粒细胞浸润和细胞因子谱,以探究 RSV 感染引起哮喘恶化的发病机制。
卵清蛋白(OVA)致敏的小鼠经 OVA 吸入 3 次后,立即用 RSV(10(5)TCID50(组织培养感染剂量的 50%)/25g 体重)或模拟感染进行感染。每组动物(对照组,PBS 代替 OVA 吸入和模拟感染;RSV 组,PBS 加 RSV;OVA 组,OVA 加模拟感染;OVA/RSV 组,OVA 加 RSV)进行分析。分析包括气道对乙酰甲胆碱的反应性评估、苏木精和伊红(HE)和 Luna 染色的气道病理变化、支气管肺泡灌洗液(BALF)和外周白细胞计数,以及 BALF 和血清中多种细胞因子/趋化因子的浓度。
与对照组相比,OVA 和 OVA/RSV 组的气道反应性明显增强。OVA 和 OVA/RSV 组的组织和 BALF 嗜酸性粒细胞水平明显高于 RSV 或对照组。与其他 3 组相比,OVA/RSV 组 BALF 中巨噬细胞炎症蛋白(MIP)-1α的水平明显升高。OVA/RSV 组血清中白细胞介素(IL)-17 的产生也明显高于对照组或 OVA 组。
这些发现表明,MIP-1α 和 IL-17 可能在 RSV 诱导的哮喘急性加重中发挥重要作用。