You Dahui, Becnel David, Wang Kai, Ripple Michael, Daly Melissa, Cormier Stephania A
Louisiana State University, Department of Biological Sciences, Baton Rouge, USA.
Respir Res. 2006 Aug 7;7(1):107. doi: 10.1186/1465-9921-7-107.
Respiratory syncytial virus (RSV) is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma.
To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 x 10(5) TCID50/g body weight) and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined.
RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-alpha levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV.
Neonatal RSV exposure results in long term pulmonary inflammation and exacerbates allergic airways disease. The early increase in TNF-alpha in the bronchoalveolar lavage implicates this inflammatory cytokine in orchestrating these events. Finally, the data presented emphasize IL-13 and TNF-alpha as potential therapeutic targets for treating RSV induced-asthma.
呼吸道合胞病毒（RSV）是婴儿和老年人急性细支气管炎最常见的病因。此外，流行病学数据表明，婴儿期感染RSV是随后发生喘息和哮喘的有力诱因。然而，RSV导致哮喘的机制复杂，在很大程度上仍不清楚。最近一项研究表明，初次感染RSV的年龄是决定气道对RSV再次激发反应的关键因素。我们推测，新生儿发育期间严重的RSV感染会显著改变肺结构和肺部免疫微环境；因此，新生儿RSV感染在诸如哮喘等过敏性炎症性疾病的发生或易感性方面至关重要。
为了研究这一假设，本研究在RSV诱导的肺部炎症和气道功能障碍的新生小鼠模型中进行。7日龄小鼠感染RSV（2×10⁵半数组织培养感染剂量/克体重），并使其发育至成年。为了确定新生儿RSV感染是否使成年动物对过敏原的病理生理反应增强，随后用卵清蛋白对这些小鼠进行致敏和激发。检测了包括肺功能、组织病理学、细胞因子产生以及支气管肺泡灌洗中的细胞成分等各种终点指标。
仅新生儿期感染RSV就导致成年期出现以气道高反应性、支气管周围和血管周围炎症以及上皮下纤维化为特征的炎症性气道疾病。如果早期RSV感染后再接触过敏原，这种肺部表型会加剧。对新生儿RSV感染的初始反应导致支气管肺泡灌洗中肿瘤坏死因子-α（TNF-α）水平升高。有趣的是，在初次感染RSV近三个月后观察到白细胞介素-13（IL-13）水平升高和黏液过度产生。
新生儿期接触RSV会导致长期肺部炎症，并加剧过敏性气道疾病。支气管肺泡灌洗中TNF-α的早期升高表明这种炎症细胞因子在协调这些事件中起作用。最后，所呈现的数据强调IL-13和TNF-α作为治疗RSV诱导的哮喘的潜在治疗靶点。
