Kameda Hideto, Suzuki Miyuki, Takeuchi Tsutomu
Division of Rheumatology/Clinical Immunology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
Drug Target Insights. 2007;2:239-47. Epub 2007 Oct 30.
Some systemic rheumatic diseases and disorders, especially fibrotic and vascular disorders, are often refractory to corticosteroid therapy. Recently, ever accumulating evidence suggests that platelet-derived growth factor (PDGF) is involved in those refractory diseases. Imatinib mesylate inhibits the activation of PDGF receptor as well as c-Abl, Bcr-Abl and c-Kit tyrosine kinases. It has therefore been widely used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells both in vitro and in vivo. Additionally, it has recently been reported that some patients with rheumatoid arthritis or idiopathic pulmonary arterial hypertension demonstrated a good clinical response to imatinib therapy. Imatinib may therefore overcome the limitations of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases, such as systemic sclerosis and interstitial lung diseases, without clinical intolerability.
一些全身性风湿性疾病和病症，尤其是纤维化和血管性病症，通常对皮质类固醇疗法难治。最近，越来越多的证据表明血小板衍生生长因子（PDGF）参与了这些难治性疾病。甲磺酸伊马替尼抑制PDGF受体以及c-Abl、Bcr-Abl和c-Kit酪氨酸激酶的激活。因此，它已被广泛用于治疗慢性髓性白血病和胃肠道间质瘤。伊马替尼在体外和体内均能有效抑制成纤维细胞、系膜细胞和平滑肌细胞的激活和增殖。此外，最近有报道称，一些类风湿性关节炎或特发性肺动脉高压患者对伊马替尼治疗表现出良好的临床反应。因此，伊马替尼可能克服目前使用皮质类固醇和免疫抑制剂治疗难治性疾病（如系统性硬化症和间质性肺病）的治疗策略的局限性，且无临床不耐受性。
