哮喘联盟

   摘要
   背景：病毒感染是导致哮喘发作的最常见原因，与气道反应性（AR）和炎症增加相关。与单纯卵清蛋白（OVA）或呼吸道合胞病毒（RSA）处理小鼠相比，OVA诱导的过敏性气道炎症（OVA/RSV）下，呼吸道合胞病毒（RSV）能增加AR。此外，白介素17A（IL-17A）仅在OVA/RSV小鼠中增加。
   目的：研究IL-17A是否能增加OVA/RSV动物的AR和炎症。
   方法：野生型（WT）BALB/c小鼠和IL-17A基因敲除（KO）小鼠分为对照组、RSV组、OVA组和OVA/RSV组。感染后收集肺组织、支气管肺泡关系液（BALF）和/或纵膈淋巴结（MLNs）。采用ELISA检测肺和BALF中的细胞因子表达。MLN采用OVA（323-229）肽或RSV M2（127-135）肽再次刺激，检测IL-17A蛋白表达。通过乙酰甲胆碱激发测试检测AR。
   结果：感染6天后，RSV能增加OVA特异性T细胞的IL-17A蛋白表达。与RSV小鼠相比，OVA/RSV小鼠干扰素-β蛋白表达下降。与对照组、OVA组和RSV组小鼠相比，OVA/RSV小鼠肺组织匀浆液IL-23p19 mRNA表达增加。意外的是，与WT OVA/RSV 小鼠相比，IL-17A KO的OVA/RSV小鼠AR增加。此外，与WT OVA/RSV相比，IL-17A KO的OVA/RSV小鼠BALF的嗜酸性粒细胞、淋巴细胞和IL-13蛋白表达增加。
   结论：IL-17A能负向调节OVA/RSV小鼠的AR和气道炎症。该结果非常重要，因为IL-17A被认为是潜在的哮喘治疗靶点，抑制IL-17A有助于改善病毒诱导的哮喘发作。
 

（刘国梁 审校）
Thorax. 2013 Feb 19. doi: 10.1136/thoraxjnl-2012-202404. [Epub ahead of print]
 

IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation.
 
Newcomb DC, Boswell MG, Reiss S, Zhou W, Goleniewska K, Toki S, Harintho MT, Lukacs NW, Kolls JK, Peebles RS Jr.

Source
Department of Medicine, Vanderbilt University Medical Center, , Nashville, Tennessee, USA.

Abstract
BACKGROUND: Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV) had increased AR compared with OVA or RSV mice alone. Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice.
OBJECTIVE: To determine whether IL-17A increases AR and inflammation in the OVA/RSV model.
METHODS: Wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were harvested after infection. Cytokine expression was determined by ELISA in the lungs or BAL fluid. MLNs were restimulated with either OVA (323-229) peptide or RSV M2 (127-135) peptide and IL-17A protein expression was analysed. AR was determined by methacholine challenge.
RESULTS: RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had decreased interferon-β protein expression compared with RSV mice. OVA/RSV mice had increased IL-23p19 mRNA expression in lung homogenates compared with mock, OVA or RSV mice. Unexpectedly, IL-17A KO OVA/RSV mice had increased AR compared with WT OVA/RSV mice. Furthermore, IL-17A KO OVA/RSV mice had increased eosinophils, lymphocytes and IL-13 protein expression in BAL fluid compared with WT OVA/RSV mice.
CONCLUSIONS: IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. This finding is important because IL-17A has been identified as a potential therapeutic target in asthma, and inhibiting IL-17A in the setting of virally-induced asthma exacerbations may have adverse consequences.
 

Thorax. 2013 Feb 19. doi: 10.1136/thoraxjnl-2012-202404. [Epub ahead of print]