Prevention and reversal of pulmonary inflammation and airway hyperresponsiveness by dexamethasone treatment in a murine model of asthma induced by house dust
Prevention and reversal of pulmonary inflammation and airway hyperresponsiveness by dexamethasone treatment in a murine model of asthma induced by house dust
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DOI：
10.1152/ajplung.00433.2003
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发表时间：
2004-09-01
影响因子：
4.9
通讯作者：
Remick, DG
中科院分区：
文献类型：
--
作者：
Kim, J;McKinley, L;Remick, DG
过去 20 年来，西方世界哮喘的发病率和死亡率增加了 75%。最近的研究表明，对蟑螂过敏原的敏感性与成人和儿童哮喘发病率的增加密切相关。我们研究了在过敏原激发之前或之后施用地塞米松是否会抑制由含有高水平蟑螂过敏原的室内灰尘提取物诱发的哮喘小鼠模型的肺部炎症和气道高反应性。对于预防实验，在每次肺部攻击前1小时对小鼠腹腔注射地塞米松，并在最后一次攻击后24小时测量气道高反应性。最后一次挑战后 48 小时处死小鼠。对于逆转研究，在最后一次攻击后 24 小时测量气道高反应性，并用地塞米松治疗小鼠。与 PBS 治疗的小鼠相比，过敏原攻击前的地塞米松治疗显着降低了肺部炎症细胞的募集、肺部髓过氧化物酶活性、气道高反应性和总血清 IgE 水平。此外，地塞米松治疗可以显着降低已确定的哮喘反应的气道高反应性。这些结果表明，地塞米松不仅可以预防而且可以终止由含有蟑螂过敏原的室内灰尘引起的哮喘反应。该模型表现出人类哮喘的几个特征，可用于病理生理机制和潜在治疗干预的研究。
The morbidity and mortality from asthma in the Western world have increased 75% in the past 20 years. Recent studies have demonstrated that sensitization to cockroach allergens correlates strongly with the increased asthma morbidity for adults and children. We investigated whether dexamethasone administered before or after allergen challenge would inhibit the pulmonary inflammation and airway hyperresponsiveness in a mouse model of asthma induced by a house dust extract with high levels of cockroach allergens. For the prevention experiment, mice were treated with an intraperitoneal injection of dexamethasone 1 h before each pulmonary challenge, and airway hyperresponsiveness was measured 24 h after the last challenge. Mice were killed 48 h after the last challenge. For the reversal study, airway hyperresponsiveness was measured 24 h after the last challenge, and the mice were treated with dexamethasone. Dexamethasone treatment before allergen challenge significantly reduced the pulmonary recruitment of inflammatory cells, myeloperoxidase activity in the lung, airway hyperreactivity, and total serum IgE levels compared with PBS-treated mice. Additionally, dexamethasone treatment could significantly reduce the airway hyperreactivity of an established asthmatic response. These results demonstrate that dexamethasone not only prevents but also halts the asthmatic response induced by house dust containing cockroach allergens. This model exhibits several features of human asthma that may be exploited in the study of pathophysiological mechanisms and potential therapeutic interventions.