Oda H, Kadota J, Kohno S, Hara K
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Chest. 1994 Oct;106(4):1116-23. doi: 10.1378/chest.106.4.1116.
The efficacy of low dose long-term erythromycin (EM) therapy in the treatment of chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB), has been reported, but its therapeutic mechanism is still unclear. In 13 patients receiving oral EM therapy the accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly reduced (p < 0.05), this reduction corresponds with an improvement in clinical symptoms. We sought to determine whether neutrophil chemotactic activity (NCA) in lavage fluid obtained from these 13 patients with DPB would respond to EM therapy. Pretreatment NCA in all patients was significantly elevated compared with levels in normal healthy nonsmoking volunteers (p < 0.001), and the level was greatly reduced after EM therapy (p < 0.001). In addition, this reduction correlated with increased percentages of neutrophils in the BAL fluid (r = 0.737, p < 0.01). Gel-filtration chromatography was also performed to characterize chemotactic factors. Pre-EM treatment BAL fluid revealed four NCA peaks (about molecular weight 15,000, 8,000, 1,500, and 300 daltons) in the elution profile, and chemotactic activity was reduced in all areas after EM therapy. These findings indicate that NCA in lavage fluid from patients with DPB consists of various components. Although it was not clear which component is predominantly affected, these results indicate that EM may inhibit the migration of neutrophils to inflammatory sites by reducing the intrapulmonary chemotactic gradient, thus, ultimately reducing pulmonary inflammation.
低剂量长期使用红霉素(EM)治疗包括弥漫性泛细支气管炎(DPB)在内的慢性下呼吸道疾病的疗效已有报道,但其治疗机制仍不清楚。在13例接受口服EM治疗的患者中,支气管肺泡灌洗(BAL)液中中性粒细胞的积聚显著减少(p<0.05),这种减少与临床症状的改善相对应。我们试图确定从这13例DPB患者获得的灌洗液中的中性粒细胞趋化活性(NCA)是否会对EM治疗产生反应。所有患者治疗前的NCA与正常健康不吸烟志愿者的水平相比显著升高(p<0.001),EM治疗后该水平大幅降低(p<0.001)。此外,这种降低与BAL液中中性粒细胞百分比的增加相关(r=0.737,p<0.01)。还进行了凝胶过滤色谱法以表征趋化因子。EM治疗前的BAL液在洗脱图谱中显示出四个NCA峰(分子量约为15,000、8,000、1,500和300道尔顿),EM治疗后所有区域的趋化活性均降低。这些发现表明,DPB患者灌洗液中的NCA由多种成分组成。虽然尚不清楚哪种成分受到的影响最大,但这些结果表明,EM可能通过降低肺内趋化梯度来抑制中性粒细胞向炎症部位的迁移,从而最终减轻肺部炎症。