Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Part Fibre Toxicol. 2009 Aug 14;6:22. doi: 10.1186/1743-8977-6-22.
Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA) male C57BL/6 mice were instilled with diesel exhaust particles (DEP) or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production.
Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1alpha, but not IL-10, RANTES, and MCP-1 in lung homogenates.
These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation.
病毒感染和接触氧化剂空气污染物是哮喘恶化的两个最重要的诱因。我们之前的研究表明，暴露于柴油机废气会增加上皮细胞体外和体内小鼠对流感病毒感染的易感性。因此，我们研究了在过敏性哮喘的情况下，接触氧化剂空气污染物是否会增加对呼吸道病毒感染的易感性，进而导致病毒引起的哮喘恶化增加。卵清蛋白致敏（OVA）雄性 C57BL/6 小鼠被注入柴油机废气颗粒（DEP）或生理盐水，24 小时后感染流感病毒 A/PR/8。感染后 24 小时处死动物，并分析肺损伤、过敏炎症和促炎细胞因子产生的标志物。
暴露于 DEP 或单独感染流感对损伤或过敏炎症标志物没有显著影响。然而，暴露于 DEP 并随后感染流感的 OVA 致敏小鼠的肺灌洗液和组织中的嗜酸性粒细胞水平增加。此外，在感染流感之前暴露于 DEP 的 OVA 致敏小鼠中，Th2 型细胞因子（如 IL-4 和 IL-13）和嗜酸性粒细胞趋化因子（如 CCL11 和 CCR3）的标志物增加。这些小鼠的肺匀浆中还显示出高水平的 IL-1alpha，但不是 IL-10、RANTES 和 MCP-1。
这些数据表明，在过敏性哮喘的情况下，暴露于柴油机废气可能会增强病毒引起的过敏炎症恶化。
