Swedin L, Neimert-Andersson T, Hjoberg J, Jonasson S, van Hage M, Adner M, Ryrfeldt A, Dahlén S-E
The National Institute of Environmental Medicine, Division of Physiology, Scheeles väg 1, Box 287, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Eur Respir J. 2009 Jul;34(1):200-8. doi: 10.1183/09031936.00030908. Epub 2009 Feb 27.
The aim of the current study was to define how cyclooxygenase (COX)-activity affects airway hyperresponsiveness (AHR) and inflammation using interventions with COX inhibitors at different time points during allergen challenge and/or prior to measurement of AHR in an eosinophil-driven allergic mouse model. Inflammatory cells were assessed in bronchioalveolar lavage (BAL) and AHR was evaluated as the total lung resistance to methacholine (MCh) challenge. Administration of FR122047 (COX-1 inhibitor) during ovalbumin (OVA) challenge and prior to MCh challenge enhanced AHR without affecting the inflammatory cell response. In contrast, administration of lumiracoxib (COX-2 inhibitor) during the same time period had no effect on AHR but reduced the inflammatory cells in BAL. Nonselective COX inhibition with diclofenac both enhanced the AHR and reduced the inflammatory cells. Administration of diclofenac only during OVA challenge reduced the cells in BAL without any changes in AHR, whereas administration of diclofenac only prior to MCh challenge enhanced AHR but did not affect the cells in BAL. The present study implicates distinct roles of prostanoids generated along the COX-1 and COX-2 pathways and, furthermore, that inflammatory cells in BAL do not change in parallel with AHR. These findings support the fact that AHR and the inflammatory response are distinct and, at least in part, uncoupled events.
本研究的目的是在嗜酸性粒细胞驱动的过敏性小鼠模型中，通过在过敏原激发的不同时间点和/或在测量气道高反应性（AHR）之前使用环氧化酶（COX）抑制剂进行干预，来确定COX活性如何影响气道高反应性和炎症。在支气管肺泡灌洗（BAL）中评估炎症细胞，并将AHR评估为肺对乙酰甲胆碱（MCh）激发的总阻力。在卵清蛋白（OVA）激发期间和MCh激发之前给予FR122047（COX-1抑制剂）可增强AHR，但不影响炎症细胞反应。相比之下，在同一时期给予氯美昔布（COX-2抑制剂）对AHR没有影响，但减少了BAL中的炎症细胞。双氯芬酸的非选择性COX抑制既增强了AHR，又减少了炎症细胞。仅在OVA激发期间给予双氯芬酸可减少BAL中的细胞，而AHR无任何变化，而仅在MCh激发之前给予双氯芬酸可增强AHR，但不影响BAL中的细胞。本研究表明COX-1和COX-2途径产生的前列腺素具有不同的作用，此外，BAL中的炎症细胞与AHR并非平行变化。这些发现支持了AHR和炎症反应是不同的，并且至少部分是不相关的事件这一事实。
