Peebles R S, Sheller J R, Johnson J E, Mitchell D B, Graham B S
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
J Med Virol. 1999 Feb;57(2):186-92. doi: 10.1002/(sici)1096-9071(199902)57:2<186::aid-jmv17>3.0.co;2-q.
Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization and RSV infection to begin exploring the immunologic interactions between allergic and virus-induced airway inflammation and its impact on airway hypersensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infection alone did not cause significant airway hyperresponsiveness (AHR) to methacholine. Ovalbumin (OVA)-induced AHR lasted only a few days past the discontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock infected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had significantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic analysis confirmed an increased inflammation in the lungs of OVA/RSV mice compared with OVA mice. In addition, OVA/RSV mice had a more widespread distribution of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of lymphocytes in BAL fluid, increased lung inflammation, and mucus deposition in the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity.
严重呼吸道合胞病毒（RSV）引发的疾病与儿童哮喘和特应性相关。我们结合了变应原致敏和RSV感染模型，以开始探索变应性和病毒诱导的气道炎症之间的免疫相互作用及其对气道高反应性的影响。通过全身体积描记法在气管插管小鼠中进行乙酰甲胆碱激发后测量气道阻力。通过支气管肺泡灌洗（BAL）和组织病理学评估肺部炎症。单独的RSV感染不会导致对乙酰甲胆碱的显著气道高反应性（AHR）。在卵清蛋白致敏并假感染的小鼠中，卵清蛋白（OVA）诱导的AHR在停止OVA气雾剂后仅持续几天。相比之下，在OVA气雾剂治疗期间感染RSV的OVA致敏小鼠（OVA/RSV）在感染后2周以上仍有AHR。然而，在RSV或假感染2周后，OVA/RSV小鼠在BAL期间发现的淋巴细胞明显多于OVA小鼠，而OVA和OVA/RSV组的嗜酸性粒细胞数量相同。组织病理学分析证实，与OVA小鼠相比，OVA/RSV小鼠肺部炎症增加。此外，与其他组相比，OVA/RSV小鼠气道中黏液分布更广泛，管腔内黏液池数量增加。因此，在卵清蛋白致敏期间，RSV感染小鼠中延长的AHR与BAL液中淋巴细胞数量增加、肺部炎症增加和气道黏液沉积相关，但与气道嗜酸性粒细胞增多无关。对变应性和病毒诱导的气道炎症联合的免疫后果的进一步了解将影响与气道高反应性相关疾病的管理。
