Danahay H, Broadley K J, McCabe P J, Nials A T, Sanjar S
Department of Pharmacology, Welsh School of Pharmacy, Cardiff University, Wales, UK.
Inflamm Res. 1999 Jan;48(1):41-7. doi: 10.1007/s000110050391.
The aim was to determine the time courses for the changes in airway function, airway reactivity, influx of inflammatory cells and levels of the pro-inflammatory cytokines, interleukin (IL)-5 and IL-8 in bronchoalveolar lavage fluid (BALF), and the plasma levels of cortisol and ACTH after antigen challenge to determine whether a temporal link could be established between these events.
Airway function was measured as specific airway conductance (sGsw) in conscious ovalbumin (OvA)-sensitized guinea pigs using whole body plethysmography at intervals after an inhalation challenge with ovalbumin (0.5% for 10 min). Airway responses to the inhaled spasmogen, U46619 (30 ng/ml, 60 s), were measured at 3, 6 and 24 h after challenge. In separate animals, bronchoalveolar lavage fluid (BALF) was obtained after anaesthetic overdose either before challenge or at 1, 3, 6, 12, or 24 h after OvA challenge. Total and differential cell counts of eosinophils and neutrophils were performed on BALF and levels of IL-5 and IL-8 determined by scintillation proximity assays and ELISA, respectively. Plasma cortisol and ACTH levels were determined by RIA kits in blood removed by cardiac puncture at intervals after challenge.
An early phase bronchoconstriction occurred which resolved by 3 h and was followed by a late phase between 17 and 24 h. Airway hyperresponsiveness to inhaled U46619, was evident at 3, 6 and 24 h after antigen challenge. Increased IL-5[BALF] was observed by 60 min post challenge implicating a performed storage site. In contrast, IL-8[BALF] was not raised until 3 h post challenge. There was a significant infiltration of neutrophils and eosinophils by 3 and 6 h, respectively. IL-5[BALF] further increased up to 24 h, during the appearance of the late phase of bronchoconstriction and whilst eosinophilia was maximal. Plasma cortisol levels were increased 1 and 3 hours after antigen challenge, thereafter returning to baseline levels.
The hyperresponsiveness appears to be dissociated from the appearance of eosinophils in lavage fluid. The early appearance of IL-5, however, could be a trigger for the migration of eosinophils and development of hyper-responsiveness. The increased plasma cortisol levels occurring after antigen challenge were presumably due to the stress involved and these would be expected to exert an endogenous anti-inflammatory effect.
目的是确定抗原激发后气道功能、气道反应性、炎症细胞浸润以及支气管肺泡灌洗液（BALF）中促炎细胞因子白细胞介素（IL）-5和IL-8水平的变化时间进程，以及皮质醇和促肾上腺皮质激素（ACTH）的血浆水平，以确定这些事件之间是否能建立时间联系。
在清醒的卵清蛋白（OvA）致敏豚鼠中，使用全身体积描记法，在吸入卵清蛋白（0.5%，持续10分钟）激发后，定期测量气道功能，以特异性气道传导率（sGsw）表示。在激发后3、6和24小时测量气道对吸入的致痉剂U46619（30 ng/ml，60秒）的反应。在另一组动物中，在麻醉过量后，于激发前或OvA激发后1、3、6、12或24小时获取支气管肺泡灌洗液（BALF）。对BALF进行嗜酸性粒细胞和中性粒细胞的总数及分类计数，并分别通过闪烁邻近分析和酶联免疫吸附测定法测定IL-5和IL-8的水平。在激发后定期通过心脏穿刺取血，使用放射免疫分析试剂盒测定血浆皮质醇和ACTH水平。
出现了早期支气管收缩，在3小时时缓解，随后在17至24小时之间出现晚期收缩。抗原激发后3、6和24小时，气道对吸入的U46619的高反应性明显。激发后60分钟观察到BALF中IL-5升高，提示存在预先储存部位。相比之下，BALF中IL-8直到激发后3小时才升高。分别在3小时和6小时时，中性粒细胞和嗜酸性粒细胞出现明显浸润。在支气管收缩晚期出现且嗜酸性粒细胞增多达到峰值时，BALF中IL-5持续升高至24小时。抗原激发后1小时和3小时血浆皮质醇水平升高，此后恢复到基线水平。
高反应性似乎与灌洗液中嗜酸性粒细胞的出现无关。然而，IL-5的早期出现可能是嗜酸性粒细胞迁移和高反应性发展的触发因素。抗原激发后血浆皮质醇水平升高可能是由于应激所致，预计这些会发挥内源性抗炎作用。
