Khair O A, Devalia J L, Abdelaziz M M, Sapsford R J, Davies R J
Dept of Respiratory Medicine, St. Bartholomew's Hospital, London, UK.
Eur Respir J. 1995 Sep;8(9):1451-7.
Although several studies have demonstrated that low-dose, long-term erythromycin treatment is effective in the management of patients with chronic lower respiratory tract infections, such as chronic bronchitis, bronchiolitis and bronchiectasis, the mechanisms underlying the action of erythromycin are not clear. We have cultured human bronchial epithelial cells (HBEC) as explant cultures from surgical tissue, and have investigated the effect of erythromycin on H. influenzae endotoxin (HIE)-induced release of inflammatory mediators in these cultures. Confluent epithelial cell cultures were incubated with 100 micrograms.mL-1 HIE +/- 0.1-10 micrograms.mL-1 erythromycin and were investigated for interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) released into the culture medium after 24 h. HIE significantly increased the release of IL-6 from 3.9 +/- 1.5 pg.micrograms-1 cellular protein (in control untreated cultures) to 12.1 +/- 1.5 pg.micrograms-1 cellular protein, and IL-8 from 83.7 +/- 8.2 pg.micrograms-1 cellular protein (in control cultures) to 225.7 +/- 44.8 pg.micrograms-1 cellular protein. Similarly, HIE led to a significantly greater release of sICAM-1 from 0.04 +/- 0.01 ng.microgram-1 cellular protein, in control cultures, to 3.8 +/- 0.9 ng.microgram-1 cellular protein. Incubation of the epithelial cultures in the presence of 0.1-10 micrograms.mL-1 erythromycin significantly blocked the HIE-induced release of IL-6, IL-8, and sICAM-1, at all concentrations of erythromycin investigated. Erythromycin also attenuated neutrophil chemotaxis and adhesion to human endothelial cells, mediated by incubation with conditioned medium obtained from HIE-exposed epithelial cell cultures, in vitro. These results suggest that H. influenzae-induced release of inflammatory mediators from airway epithelial cells could contribute to chronic airway inflammation, and that this effect may be modulated by treatment with erythromycin.
尽管多项研究表明，低剂量长期使用红霉素治疗对慢性下呼吸道感染患者（如慢性支气管炎、细支气管炎和支气管扩张症）的管理有效，但红霉素作用的潜在机制尚不清楚。我们从手术组织中培养了人支气管上皮细胞（HBEC）作为外植体培养物，并研究了红霉素对这些培养物中流感嗜血杆菌内毒素（HIE）诱导的炎症介质释放的影响。将汇合的上皮细胞培养物与100微克·毫升-1的HIE ± 0.1 - 10微克·毫升-1的红霉素一起孵育，并在24小时后检测释放到培养基中的白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和可溶性细胞间粘附分子-1（sICAM-1）。HIE显著增加了IL-6的释放，从（未处理的对照培养物中）3.9 ± 1.5皮克·微克-1细胞蛋白增加到12.1 ± 1.5皮克·微克-1细胞蛋白，以及IL-8的释放，从（对照培养物中）83.7 ± 8.2皮克·微克-1细胞蛋白增加到225.7 ± 44.8皮克·微克-1细胞蛋白。同样，HIE导致sICAM-1的释放显著增加，从对照培养物中的0.04 ± 0.01纳克·微克-1细胞蛋白增加到3.8 ± 0.9纳克·微克-1细胞蛋白。在所研究的所有红霉素浓度下，上皮细胞培养物在0.1 - 10微克·毫升-1红霉素存在下孵育显著阻断了HIE诱导的IL-6、IL-8和sICAM-1的释放。在体外，通过与从暴露于HIE 的上皮细胞培养物中获得的条件培养基孵育，红霉素还减弱了中性粒细胞趋化性和对人内皮细胞的粘附。这些结果表明，流感嗜血杆菌诱导气道上皮细胞释放炎症介质可能导致慢性气道炎症，并且这种作用可能通过红霉素治疗得到调节。
