Investigation to determine the cause of interstitial pneumonia by the EGFR inhibitors, and the development of that suppression method

急性间质性肺炎是表皮生长因子受体（EGFR）抑制剂的严重副作用之一，但其原因尚不清楚。在这里，我们报道用EGFR抑制剂治疗的癌细胞诱导正常肺细胞纤维化。用EGFR-酪氨酸激酶抑制剂（AG1478）或EGFR抗体培养人舌鳞癌（HSC-3）。EGFR抑制剂可提高HSC-3中IL-6的表达水平。这些上清液作为条件培养基。然后用条件培养基培养正常人肺成纤维细胞样细胞系OUS-11。我们检测了作为纤维化标志的胶原蛋白的表达，以确定us -11是否诱导了纤维化。结果表明，条件培养基处理的us -11细胞中胶原蛋白的表达水平高于对照细胞。这些数据表明，急性间质性肺炎是由EGFR抑制剂处理的癌细胞诱导的IL-6。

Acute interstitial pneumonia is one of serious side effects of epidermal growth factor receptor (EGFR) inhibitor, although that cause is still unknown. Here we report that cancer cells treated with EGFR inhibitors induce fibrosis of normal lung cell. Human tangue squamous cell carcinoma (HSC-3) was cultured with EGFR-tyrosine kinase inhibitor (AG1478) or EGFR antibody. IL-6 expression level was elevated by EGFR inhibitors in HSC-3. Those supernatants were used as the conditioned medium. Then, OUS-11, normal human lung fibroblast-like cell line, was cultured with the conditioned medium. We investigated the expression of collagen, which was the marker for fibrosis, to confirm whether fibrosis was induced or not in OUS-11. That result showed that the expression level of collagen in OUS-11 treated with conditioned medium was higher than control cells. These data suggested that acute interstitial pneumonia was induced IL-6 from cancer cells treated with EGFR inhibitors.