Sugiyama H, Okada C, Bewtra A K, Hopp R J, Townley R G
Allergic Disease Center, Creighton University, Omaha, Neb. 68178.
J Allergy Clin Immunol. 1992 Apr;89(4):858-66. doi: 10.1016/0091-6749(92)90442-5.
We investigated the effects of formoterol, a new, long-acting, selective beta 2-adrenoceptor agonist, on the antigen-induced late asthmatic response (LAR) and airway inflammation in guinea pigs. Animals were sensitized by exposure to aerosolized ovalbumin (2% in saline). After antigen challenge, preceded by administration of an H1-receptor antagonist, specific airway conductance was measured with a two-chambered whole-body plethysmograph. An aerosolized solution of formoterol, isoproterenol, or saline was inhaled 15 minutes before challenge. Bronchoalveolar lavage (BAL) was performed 24 hours after challenge. The provocative concentrations of histamine required to decrease specific airway conductance by 50% were obtained before challenge, at 24 hours, and at 72 hours after challenge. The LAR (52.7% +/- 7.7% of the baseline; p less than 0.02) was observed 6 to 8 hours after antigen challenge. An increased cellular influx in BAL (mainly eosinophils and macrophages) and an increased bronchial responsiveness to histamine occurred 24 hours after antigen challenge. Formoterol completely inhibited the LAR and the cellular increase in BAL; however, isoproterenol failed to prevent either the cellular infiltration or the LAR. Formoterol also decreased the antigen-induced increase in bronchial reactivity. These findings suggest that formoterol has inhibitory effects on the underlying inflammatory processes in antigen-induced asthma in addition to prolonged bronchodilation.
我们研究了新型长效选择性β2肾上腺素能受体激动剂福莫特罗对豚鼠抗原诱导的迟发性哮喘反应(LAR)和气道炎症的影响。通过暴露于雾化的卵清蛋白(盐水中2%)使动物致敏。在抗原激发前给予H1受体拮抗剂后,用双腔全身体积描记器测量特异性气道传导率。在激发前15分钟吸入福莫特罗、异丙肾上腺素或盐水的雾化溶液。激发后24小时进行支气管肺泡灌洗(BAL)。在激发前、激发后24小时和72小时获得使特异性气道传导率降低50%所需的组胺激发浓度。抗原激发后6至8小时观察到迟发性哮喘反应(为基线的52.7%±7.7%;p<0.02)。抗原激发后24小时,支气管肺泡灌洗中的细胞流入增加(主要是嗜酸性粒细胞和巨噬细胞),并且支气管对组胺的反应性增加。福莫特罗完全抑制了迟发性哮喘反应和支气管肺泡灌洗中的细胞增加;然而,异丙肾上腺素未能预防细胞浸润或迟发性哮喘反应。福莫特罗还降低了抗原诱导的支气管反应性增加。这些发现表明,福莫特罗除了具有延长的支气管舒张作用外,还对抗原诱导的哮喘潜在炎症过程具有抑制作用。