Devalia J L, Rusznak C, Abdelaziz M M, Davies R J
Department of Asthma and Allergic Respiratory Diseases, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London Chest Hospital, United Kingdom.
J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S51-7; discussion S64-6.
We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.
我们开展了一系列研究，调查奈多罗米钠的抗炎作用，特别关注其在体外对人支气管上皮细胞和嗜酸性粒细胞以及在体内对嗜酸性粒细胞的影响。奈多罗米钠对臭氧诱导的人支气管上皮细胞释放白细胞介素-8产生剂量相关的抑制作用，还可减弱粒细胞巨噬细胞集落刺激因子、肿瘤坏死因子-α和可溶性细胞间黏附分子1的释放。来自人支气管上皮细胞培养物的培养基含有促炎细胞因子白细胞介素-8、粒细胞巨噬细胞集落刺激因子、“活化正常T细胞表达和分泌”、白细胞介素-1β和肿瘤坏死因子-α，可增加嗜酸性粒细胞趋化性以及嗜酸性粒细胞对培养的人内皮细胞的黏附。在奈多罗米钠存在的情况下，趋化性和增加的黏附被阻断。该药物还消除了由活化嗜酸性粒细胞存在诱导的上皮细胞功能障碍（以纤毛摆动频率评估），并阻断了嗜酸性粒细胞阳离子蛋白从嗜酸性粒细胞的释放。我们还进行了一项双盲安慰剂对照研究，观察每日4次、连续16周给予常规沙丁胺醇200微克或奈多罗米钠4毫克对支气管活检和支气管肺泡灌洗样本中炎症细胞数量的影响。根据活检样本中的总嗜酸性粒细胞和活化嗜酸性粒细胞进行评估，使用奈多罗米钠时炎症减轻，与使用沙丁胺醇时的恶化情况有显著差异，尽管这两种变化与安慰剂治疗相比均无显著差异。支气管肺泡灌洗样本中嗜酸性粒细胞阳离子蛋白水平呈现类似趋势。
