Department of Pediatrics, University of California, Irvine, Irvine, California 92697-4560, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Apr;300(4):R917-24. doi: 10.1152/ajpregu.00270.2010. Epub 2011 Jan 12.
Exercise-induced bronchoconstriction (EIB) is common; however, key aspects of its pathogenesis are still unclear. We investigated the feasibility of adapting an established animal model of asthma to investigate the earliest stages of EIB. The hypothesis was that a single exposure to a normally innocuous, and brief, exercise challenge could trigger EIB symptoms in rats previously sensitized to ovalbumin (OVA) but otherwise unchallenged. Brown-Norway rats were sensitized by intraperitoneal injection of OVA at 0 and 2 wk. At week 3, animals were exposed to either aerosolized OVA (SS) or exercise (EXS). A trained, blinded, clinical observer graded EIB by respiratory sounds. Plasma and lung cytokine levels were analyzed. No control rats with or without exercise (EX, CON) showed evidence of EIB. Eighty percent of the SS group demonstrated abnormal breath sounds upon exposure to aerosolized OVA. Approximately 30% of EXS rats sensitized to OVA but exposed only to exercise had abnormal breath sounds. Lung tissue levels of TNF-α, IL-1α, growth-related oncogene/keratinocyte/chemoattractant, and IFN-γ were significantly higher (P < 0.001) in the SS group, relative to all other groups. Changes in most of these cytokines were not notable in the EXS rats, suggesting a different mechanism of EIB. Remarkably, IFN-γ, but not the other cytokines measured, was significantly elevated following brief exercise in both sensitized and unsensitized rats. Exercise led to detectable breathing sound abnormalities in sensitized rats, but less severe than those observed following classical OVA challenge. Precisely how this immune crossover occurs is not known, but this model may be useful in elucidating essential mechanisms of EIB.
运动诱发性支气管收缩（EIB）很常见；然而，其发病机制的关键方面仍不清楚。我们研究了将已建立的哮喘动物模型改编为研究 EIB 最早阶段的可行性。假设是，先前对卵清蛋白（OVA）致敏但未受到其他挑战的大鼠，单次暴露于通常无害且短暂的运动挑战中，可能会引发 EIB 症状。Brown-Norway 大鼠通过腹腔注射 OVA 在 0 和 2 周时致敏。在第 3 周，动物暴露于雾化 OVA（SS）或运动（EXS）。一名经过培训、盲目的临床观察员通过呼吸声音对 EIB 进行分级。分析血浆和肺细胞因子水平。没有运动（EX，CON）的对照大鼠或没有运动的对照大鼠均没有出现 EIB 的迹象。SS 组中 80%的大鼠在暴露于雾化 OVA 时出现异常呼吸音。大约 30%的对 OVA 致敏但仅暴露于运动的 EXS 大鼠出现异常呼吸音。与所有其他组相比，SS 组的 TNF-α、IL-1α、生长相关癌基因/角质细胞/趋化因子和 IFN-γ的肺组织水平显着升高（P < 0.001）。在 EXS 大鼠中，这些细胞因子中的大多数变化并不明显，表明 EIB 有不同的机制。值得注意的是，IFN-γ，而不是测量的其他细胞因子，在致敏和未致敏大鼠进行短暂运动后显着升高。运动导致致敏大鼠出现可检测的呼吸音异常，但比经典 OVA 挑战后观察到的异常程度要轻。这种免疫交叉发生的确切方式尚不清楚，但这种模型可能有助于阐明 EIB 的基本机制。
