Severe equine asthma is characterized by airway hyperresponsiveness, neutrophilic inflammation and structural alterations of the lower airways. In asthmatic horses with neutrophilic inflammation, there is insensitivity to corticosteroids characterized by the persistence of neutrophils within the airways with therapy. We hypothesized that hypoxia or oxidative stress in the microenvironment of the lung contributes to this insensitivity of neutrophils to corticosteroids in asthmatic horses. Blood neutrophils isolated from horses with severe asthma (N = 8) and from healthy controls (N = 8) were incubated under different cell culture conditions simulating hypoxia and oxidative stress and, in the presence, or absence of dexamethasone. The pro-inflammatory gene and protein expression of neutrophils were studied. In both groups, pyocyanin-induced oxidative stress increased the mRNA expression of IL-8, IL-1β, and TNF-α. While IL-1β and TNF-α were downregulated by dexamethasone under these conditions, IL-8 was not. Simulated hypoxic conditions did not enhance pro-inflammatory gene expression in neutrophils from either group of horses. In conclusion, oxidative stress but not hypoxia may contribute to corticosteroid insensitivity via a selective gene regulation pathway. Equine neutrophil responses were similar in both heathy and asthmatic horses, indicating that it is not specific to asthmatic inflammation.

严重的马哮喘的特征是气道高反应性、中性粒细胞炎症和下呼吸道的结构改变。在患有中性粒细胞炎症的哮喘马中，对皮质类固醇不敏感，其特征是治疗后气道内中性粒细胞持续存在。我们假设肺微环境中的缺氧或氧化应激导致中性粒细胞对哮喘马的皮质类固醇不敏感。从患有严重哮喘的马 (N = 8) 和健康对照 (N = 8) 的马中分离出的血液中性粒细胞在模拟缺氧和氧化应激的不同细胞培养条件下，在存在或不存在地塞米松的情况下进行培养。研究了中性粒细胞的促炎基因和蛋白质表达。在两组中，绿脓素诱导的氧化应激增加了 IL-8、IL-1β 和 TNF-α 的 mRNA 表达。虽然 IL-1β 和 TNF-α 在这些条件下被地塞米松下调，但 IL-8 没有。模拟的缺氧条件不会增强两组马的中性粒细胞中促炎基因的表达。总之，氧化应激而非缺氧可能通过选择性基因调控途径导致皮质类固醇不敏感。健康马和哮喘马的中性粒细胞反应相似，表明它不是哮喘炎症的特异性反应。模拟的缺氧条件不会增强两组马的中性粒细胞中促炎基因的表达。总之，氧化应激而非缺氧可能通过选择性基因调控途径导致皮质类固醇不敏感。健康马和哮喘马的中性粒细胞反应相似，表明它不是哮喘炎症的特异性反应。模拟的缺氧条件不会增强两组马的中性粒细胞中促炎基因的表达。总之，氧化应激而非缺氧可能通过选择性基因调控途径导致皮质类固醇不敏感。健康马和哮喘马的中性粒细胞反应相似，表明它不是哮喘炎症的特异性反应。