Chapman R W, Sehring S J, Garlisi C G, Falcone A, Kung T T, Stelts D, Minnicozzi M, Jones H, Umland S, Egan R W, Kreutner W
Department of Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Arzneimittelforschung. 1998 Apr;48(4):384-91.
Mometasone furoate (CAS 83919-23-7, Sch 32088) is a new inhaled corticosteroid that is being developed to treat allergic inflammatory airway disorders such as rhinitis and asthma. In this study, we investigated the effects of inhaled mometasone furoate in allergic mice that, after antigen challenge, develop an influx of eosinophils and T cells and display an increased mRNA expression of proinflammatory cytokines in the lungs. Mometasone furoate aerosol was generated from metered dose inhalers and delivered into an animal exposure chamber. The mice were exposed to mometasone furoate by nose-only inhalation at respired doses ranging from 0.5-33 micrograms/kg given 24, 18 and 2 h before aeroallergen challenge. The elevated eosinophil numbers in the bronchoalveolar lavage fluid and lung tissues of sensitized, ovalbumin challenged mice were dose-dependently inhibited by inhaled mometasone furoate. Increased numbers of Thy1+ T cells and CD4+ (T-helper) and CD8+ (T-cytotoxic) T cell subsets were seen in the bronchoalveolar lavage fluid of ovalbumin-challenged mice. Pretreatment of these animals with mometasone furoate (33 micrograms/kg) reduced the number of Thy1+ T cells and the T-helper subset. Furthermore, mometasone furoate (33 micrograms/kg) reduced the percentage of CD44+ T-helper cells (activated/memory cells) to the levels observed in non-sensitized, ovalbumin-challenged mice. There were increased levels of steady-state mRNA for interleukin-4, interleukin-5, and to a lesser extent, gamma-interferon in the lungs of sensitized mice after ovalbumin challenge and pretreatment with mometasone furoate reduced the steady-state mRNA levels of these cytokines. Our results demonstrate a potent lung anti-inflammatory effect of inhaled mometasone furoate and identify that inhibition of T cell influx, eosinophil accumulation and modulation of cytokine activity are important components of this response.
糠酸莫米松（CAS 83919-23-7，Sch 32088）是一种新型吸入性皮质类固醇，正在研发用于治疗过敏性炎症性气道疾病，如鼻炎和哮喘。在本研究中，我们调查了吸入糠酸莫米松对过敏性小鼠的影响，这些小鼠在抗原激发后，肺部会出现嗜酸性粒细胞和T细胞流入，并表现出促炎细胞因子mRNA表达增加。糠酸莫米松气雾剂由定量吸入器产生，并输送到动物暴露舱中。在气源性变应原激发前24、18和2小时，通过仅经鼻吸入将小鼠暴露于剂量范围为0.5-33微克/千克的糠酸莫米松。吸入糠酸莫米松可剂量依赖性地抑制致敏、卵清蛋白激发小鼠支气管肺泡灌洗液和肺组织中嗜酸性粒细胞数量的增加。在卵清蛋白激发小鼠的支气管肺泡灌洗液中，可见Thy1+ T细胞以及CD4+（辅助性T细胞）和CD8+（细胞毒性T细胞）T细胞亚群数量增加。用糠酸莫米松（33微克/千克）对这些动物进行预处理可减少Thy1+ T细胞和辅助性T细胞亚群的数量。此外，糠酸莫米松（33微克/千克）可将CD44+辅助性T细胞（活化/记忆细胞）的百分比降低至未致敏、卵清蛋白激发小鼠中观察到的水平。卵清蛋白激发后，致敏小鼠肺中白细胞介素-4、白细胞介素-5以及程度较轻的γ-干扰素的稳态mRNA水平升高，而用糠酸莫米松预处理可降低这些细胞因子的稳态mRNA水平。我们的结果表明吸入糠酸莫米松具有强大的肺部抗炎作用，并确定抑制T细胞流入、嗜酸性粒细胞积聚和调节细胞因子活性是该反应的重要组成部分。
