Department of Bone, Respiratory, Immunology and Dermatology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA.
Pulm Pharmacol Ther. 2011 Feb;24(1):67-73. doi: 10.1016/j.pupt.2010.10.002. Epub 2010 Oct 13.
Mometasone furoate (MF)/formoterol fumarate (F) combination is a new inhaIed corticosteroid/long-acting β₂-adrenergic agonist (ICS/LABA). The purpose of this study was to evaluate the effects of different dose combinations of MF/F on a variety of late-phase responses to aerosolized antigen challenge in ovalbumin sensitized Brown Norway rats. Late-phase responses were assessed by reductions in lung function, measured by forced vital capacity (FVC) and increased numbers of inflammatory cells and pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid of ovalbumin challenged rats. Intratracheal administration of MF/F 5 h before aerosolized ovalbumin challenge inhibited the increase in inflammatory cells, including eosinophils and levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor-α (TNF-α) appearing in the bronchoalveolar lavage fluid 24 h after the antigen challenge. The combination index for inhibition of both inflammatory cells and cytokines was consistently <1 suggesting a synergistic interaction between MF and F. Intratracheal MF/F given 24 h after the aerosolized ovalbumin challenge reversed the reduction in FVC with statistically significant effects seen over a 24 h period after drug whereas MF and F alone reversed the antigen-induced reduction in FVC at selected times only. At 5 h after drug administration, when both MF and F were partially active, the combination index for MF/F was <1 suggesting a synergistic interaction between MF and F for reversal of the lung function. These results demonstrate that MF/F combination inhibits a variety of late-phase responses induced by allergen challenge and it is likely that MF/F will have a significant benefit in clinical asthma to suppress lung inflammation and improve lung function.
糠酸莫米松/富马酸福莫特罗（MF/F）联合是一种新型的吸入性皮质类固醇/长效β₂-肾上腺素能激动剂（ICS/LABA）。本研究旨在评估不同剂量组合的 MF/F 对卵清蛋白致敏的褐家鼠雾化抗原激发后各种晚期相反应的影响。晚期相反应通过雾化抗原激发后 24 小时，通过用力肺活量（FVC）的降低和支气管肺泡灌洗液（BAL）中炎症细胞和促炎细胞因子的增加来评估。MF/F 于雾化卵清蛋白激发前 5 小时气管内给药，抑制了炎症细胞的增加，包括嗜酸性粒细胞和白细胞介素（IL）-4、IL-5、IL-13 和肿瘤坏死因子-α（TNF-α）水平在抗原激发后 24 小时出现在支气管肺泡灌洗液中。抑制炎症细胞和细胞因子的组合指数均<1，提示 MF 和 F 之间存在协同作用。雾化卵清蛋白激发后 24 小时给予气管内 MF/F 逆转了 FVC 的降低，在药物后 24 小时内具有统计学意义的效果，而 MF 和 F 单独仅在选定时间逆转了抗原诱导的 FVC 降低。在药物给药后 5 小时，当 MF 和 F 都部分有效时，MF/F 的组合指数<1，提示 MF 和 F 之间存在协同作用，可逆转肺功能。这些结果表明，MF/F 联合抑制了过敏原激发引起的各种晚期相反应，MF/F 很可能在临床哮喘中具有显著的益处，可抑制肺炎症和改善肺功能。
