TY - JOUR T1 - Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-induced acute pneumonitis in mice JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3928 AU - Hironori Mikumo AU - Ichiro Inoshima AU - Saiko Ogata AU - Yuichi Mizuta AU - Kunihiro Suzuki AU - Tetsuya Yokoyama AU - Naoki Hamada AU - Yoichi Nakanishi Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3928.abstract N2 - INTRODUCTION: Gefitinib, one of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It is well known that gefitinib can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophil plays important roles in the development of the disease. (Harada C et al. Am J Respir Crit Care Med. 2011).AIMS and OBJECTIVES: The aim of this study is to investigate the effects of neutrophil elastase inhibitor sivelestat (ONO-5046) on gefitinib-induced pneumonitis in mice.METHODS: C57BL/6J mice received naphthalene (200 mg/kg) intraperitonially on day 0. Gefitinib (250 or 300 mg/kg) was orally given to mice from day 1 until 13. Sivelestat (150 mg/kg) was given intraperitoneally from day 1 until 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained on day14.RESULTS: Sivelestat treatment significantly reduced the protein level and neutrophil count in BALF, and severity of histopathologic findings on day 14 of mice given 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved survival of mice given 300 mg/kg of gefitinib.CONCLUSIONS: The present results indicate that sivelestat may be one of the promising therapeutic agents for severe acute pneumonitis caused by gefitinib. ER -