Mehta H, Sorkness R, Kaplan M R, Castleman W L, Lemanske R F
Department of Medicine, University of Wisconsin, Madison 53792-3244, USA.
Pediatr Res. 1997 Jun;41(6):872-7. doi: 10.1203/00006450-199706000-00012.
Respiratory viral infections have been associated with airway obstruction and hyperresponsiveness, and exacerbations of asthma. Although virus-induced asthma is thought to be precipitated by airway inflammation, the clinical efficacy and rationale for using antiinflammatory treatment during such exacerbations remains controversial. The purpose of this study was to use a well characterized animal model of respiratory viral illness to test the hypothesis that the inflammatory response to viral infection is responsible for the development of airway dysfunction. Adult rats were inoculated with either Sendai virus or sterile vehicle and treated with daily injections of dexamethasone or saline. At postinoculation d 4, 5, or 6, rats were evaluated for airway obstruction, hyperresponsivenes, inflammation, and lung viral titers. Saline-treated infected rats had significant airway obstruction (increased resistance, decreased dynamic compliance), hyperresponsiveness (i.v. methacholine), and inflammation (increased bronchoalveolar lavage leukocytes) compared with noninfected controls. In contrast, dexamethasone-treated infected rats had no increase in bronchoalveolar lavage leukocytes and significantly smaller changes in airway physiology, but had increased lung viral titers compared with saline-treated infected rats. We conclude that glucocorticoid suppression of the inflammatory response to respiratory viral infection largely prevents virus-associated airway dysfunction.
呼吸道病毒感染与气道阻塞、高反应性以及哮喘发作有关。尽管病毒诱发的哮喘被认为是由气道炎症引发的，但在这类发作期间使用抗炎治疗的临床疗效和理论依据仍存在争议。本研究的目的是利用一种特征明确的呼吸道病毒疾病动物模型，来检验以下假设：对病毒感染的炎症反应是气道功能障碍发展的原因。成年大鼠接种仙台病毒或无菌载体，并每日注射地塞米松或生理盐水进行治疗。在接种后第4、5或6天，对大鼠进行气道阻塞、高反应性、炎症和肺病毒滴度评估。与未感染的对照组相比，生理盐水治疗的感染大鼠出现了明显的气道阻塞（阻力增加、动态顺应性降低）、高反应性（静脉注射乙酰甲胆碱）和炎症（支气管肺泡灌洗白细胞增多）。相比之下，地塞米松治疗的感染大鼠支气管肺泡灌洗白细胞没有增加，气道生理变化明显较小，但与生理盐水治疗的感染大鼠相比，肺病毒滴度有所增加。我们得出结论，糖皮质激素对呼吸道病毒感染炎症反应的抑制作用在很大程度上可预防与病毒相关的气道功能障碍。
