Johansson Mia, Gustafsson Åsa, Johanson Gunnar, Öberg Mattias
a Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden.
b Swedish Defense Research Agency (FOI) , Umeå , Sweden.
Inhal Toxicol. 2017 Feb;29(2):82-91. doi: 10.1080/08958378.2017.1299260.
It has been suggested that asthmatics are more susceptible than healthy individuals to airborne irritating chemicals in general. However, there is limited human data available to support this hypothesis due to ethical and practical difficulties. We explored a murine model of ovalbumin (OVA)-induced airway inflammation to study susceptibility during acute exposure to chemicals with chlorine as a model substance.
Naïve and OVA sensitized female BALB/c mice were exposed to chlorine at four different concentrations (0, 5, 30 and 80 ppm) for 15 minutes with online recording of the respiratory function by plethysmography. The specific effects on respiratory mechanics, inflammatory cells and inflammatory mediators (cytokines and chemokines) of the airways were measured 24 hours after the chlorine exposure as well as histopathological examination of the lungs.
Similar concentration-dependent reductions in respiratory frequency were seen in the two groups, with a 50% reduction (RD) slightly above 5 ppm. Decreased body weight 24 hours after exposure to 80 ppm was also observed in both groups. Naïve, but not OVA-sensitized, mice showed increased bronchial reactivity and higher number of neutrophils in bronchoalveolar lavage fluid at 80 ppm.
The results do not support an increased susceptibility to chlorine among OVA-sensitized mice. This animal model, which represents a phenotype of eosinophilic airway inflammation, seems unsuitable to study susceptibility to inhalation of irritants in relation to asthma.
一般认为，哮喘患者比健康个体更容易受到空气中刺激性化学物质的影响。然而，由于伦理和实际困难，现有的人类数据有限，无法支持这一假设。我们探索了一种卵清蛋白（OVA）诱导的气道炎症小鼠模型，以研究在急性接触以氯为模型物质的化学物质期间的易感性。
将未致敏和OVA致敏的雌性BALB/c小鼠暴露于四种不同浓度（0、5、30和80 ppm）的氯中15分钟，通过体积描记法在线记录呼吸功能。在氯暴露24小时后测量对气道呼吸力学、炎症细胞和炎症介质（细胞因子和趋化因子）的具体影响，并对肺进行组织病理学检查。
两组均观察到类似的呼吸频率浓度依赖性降低，在略高于5 ppm时降低50%（RD）。两组在暴露于80 ppm后24小时体重均下降。未致敏小鼠（而非OVA致敏小鼠）在80 ppm时支气管反应性增加，支气管肺泡灌洗液中的中性粒细胞数量增多。
结果不支持OVA致敏小鼠对氯的易感性增加。这种代表嗜酸性气道炎症表型的动物模型似乎不适用于研究与哮喘相关的吸入性刺激物易感性。
