Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Biol Pharm Bull. 2010;33(6):1028-32. doi: 10.1248/bpb.33.1028.
Asthma is characterized by chronic eosinophilic inflammation and hyperresponsiveness of the airways. We hypothesized that thalidomide, which has numerous immunomodulatory properties, may have anti-inflammatory effects in allergic asthma. BALB/c mice sensitized and challenged with ovalbumin (OVA) were treated orally with thalidomide (30, 100, or 300 mg/kg) or a vehicle. When thalidomide was administered to OVA-challenged mice, the number of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly decreased. The numbers of inflammatory cells other than eosinophils were not reduced by thalidomide. Thalidomide inhibited the elevated levels of interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-alpha) in BALF by OVA challenges. Histological analysis of the lung revealed that both the infiltration of inflammatory cells and the hyperplasia of goblet cells were significantly suppressed by thalidomide treatment. Furthermore, thalidomide significantly inhibited the response to methacholine induced by OVA challenges. Taken together, thalidomide treatment decreased airway inflammation and hyperresponsiveness in a murine model of allergic asthma. These results might provide an opportunity for the development of novel therapeutics to treat severe asthma.
哮喘的特征是慢性嗜酸性粒细胞炎症和气道高反应性。我们假设，具有多种免疫调节特性的沙利度胺可能对过敏性哮喘具有抗炎作用。用卵清蛋白（OVA）致敏和激发的 BALB/c 小鼠经口给予沙利度胺（30、100 或 300mg/kg）或载体。当沙利度胺给予 OVA 激发的小鼠时，支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞数量明显减少。嗜酸性粒细胞以外的炎症细胞数量未因沙利度胺而减少。沙利度胺抑制了 OVA 激发引起的白细胞介素-5（IL-5）和肿瘤坏死因子-α（TNF-α）水平的升高。肺的组织学分析表明，沙利度胺治疗显著抑制了炎症细胞浸润和杯状细胞增生。此外，沙利度胺还显著抑制了 OVA 激发引起的乙酰甲胆碱反应。综上所述，沙利度胺治疗可降低过敏性哮喘小鼠模型的气道炎症和高反应性。这些结果可能为开发治疗严重哮喘的新型疗法提供机会。
