Hirano Atsushi, Kanehiro Arihiko, Ono Katsuichiro, Ito Wataru, Yoshida Akio, Okada Chiharu, Nakashima Hiromi, Tanimoto Yasushi, Kataoka Mikio, Gelfand Erwin W, Tanimoto Mitsune
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Am J Respir Cell Mol Biol. 2006 Sep;35(3):366-77. doi: 10.1165/rcmb.2005-0452OC. Epub 2006 May 4.
We investigated the therapeutic potential of a newly developed antifibrotic agent, pirfenidone, to regulate airway remodeling and the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenge. Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways. IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid and ovalbumin-specific serum IgE antibody levels were also significantly reduced. Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid. Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung. These data indicate that pirfenidone may play an important role in the treatment of asthma and has the potential reduce or prevent airway remodeling.
我们研究了新开发的抗纤维化药物吡非尼酮在慢性过敏原激发后调节气道重塑、过敏性气道炎症发展和气道高反应性方面的治疗潜力。在致敏后但在卵清蛋白激发期间给予吡非尼酮,可显著预防气道高反应性的发展,并防止嗜酸性粒细胞和淋巴细胞在气道中积聚。支气管肺泡灌洗液中的白细胞介素-4、白细胞介素-5和白细胞介素-13水平以及卵清蛋白特异性血清IgE抗体水平也显著降低。吡非尼酮治疗显著降低了支气管肺泡灌洗液中转化生长因子-β1和血小板衍生生长因子的水平。吡非尼酮降低了转化生长因子-β1的表达、杯状细胞增生和上皮下胶原化的发展以及肺中收缩成分的增加。这些数据表明,吡非尼酮可能在哮喘治疗中发挥重要作用,并且有可能减少或预防气道重塑。