BACKGROUND Bronchial asthma (BA) is a chronic disease of the airways. The great majority of BA exacerbations are associated with respiratory viral infections. Recent findings point out a possible role of proinflammatory cytokine interleukin-33 (IL-33) in the development of atopic diseases. Although, little is known about the role of IL-33 in virus-induced BA exacerbations. METHODS We used mouse models of RSV (respiratory syncytial virus)-induced inflammation exacerbation in OVA-sensitized mice and RSV infection alone in adult animals to characterize expression of il33 in the mouse lungs. Moreover, we studied the influence of il33 knockdown with intranasally administrated siRNA on the development of RSV-induced inflammation exacerbation. In addition, we evaluated the expression of IL33 in the ex vivo stimulated PBMCs from allergic asthma patients and healthy subjects with and without confirmed acute respiratory viral infection. RESULTS Using mouse models, we found that infection with RSV drives enhanced il33 mRNA expression in the mouse lung. Treatment with anti-il33 siRNA diminishes airway inflammation in the lungs (we found a decrease in the number of inflammatory cells in the lungs and in the severity of histopathological alterations) of mice with RSV-induced inflammation exacerbation, but do not influence viral load. Elevated level of the IL33 mRNA was detected in ex vivo stimulated blood lymphocytes of allergic asthmatics infected with respiratory viruses. RSV and rhinovirus were the most detected viruses in volunteers with symptoms of respiratory infection. CONCLUSION The present study provides additional evidence of the crucial role of the IL-33 in pathogenesis of RSV infection and virus-induced allergic bronchial asthma exacerbations.

中文翻译：

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呼吸道合胞病毒上调 OVA 致敏小鼠和哮喘受试者病毒诱导炎症恶化小鼠模型中 IL-33 的表达

背景技术支气管哮喘(BA)是一种慢性气道疾病。绝大多数 BA 恶化与呼吸道病毒感染有关。最近的研究结果指出了促炎细胞因子白细胞介素 33 (IL-33) 在特应性疾病发展中的可能作用。虽然，关于 IL-33 在病毒诱导的 BA 恶化中的作用知之甚少。方法 我们使用 RSV（呼吸道合胞病毒）诱导的 OVA 致敏小鼠炎症恶化和成年动物单独感染 RSV 的小鼠模型来表征小鼠肺中 il33 的表达。此外，我们研究了用鼻内给药的 siRNA 敲低 il33 对 RSV 诱导的炎症恶化发展的影响。此外，我们评估了来自过敏性哮喘患者和健康受试者的离体刺激的 PBMC 中 IL33 的表达，这些受试者有和没有确诊的急性呼吸道病毒感染。结果 使用小鼠模型，我们发现感染 RSV 会增强小鼠肺中的 il33 mRNA 表达。用抗 il33 siRNA 治疗可减轻 RSV 诱导的炎症恶化小鼠的肺部气道炎症（我们发现肺部炎症细胞数量减少和组织病理学改变的严重程度降低），但不影响病毒载量。在感染呼吸道病毒的过敏性哮喘患者的离体刺激的血液淋巴细胞中检测到 IL33 mRNA 水平升高。RSV 和鼻病毒是在有呼吸道感染症状的志愿者中检测到最多的病毒。