Werner U, Seitz O, Szelenyi I
Department of Pharmacology, ASTA Medica AG, Frankfurt, Germany.
Agents Actions. 1993;38 Spec No:C112-4. doi: 10.1007/BF01991154.
In the present study the effects of drugs, with different modes of action, on FMLP-stimulated release of elastase from human leukocytes were investigated in vitro. Anti-asthmatic and anti-allergic drugs were compared to well-known anti-inflammatory and anti-histamine agents. The anti-asthmatic/anti-allergic compounds azelastine, astemizole and oxatomide, and the 5-lipoxygenase inhibitor NDGA, were able to suppress the release of elastase from human leukocytes in concentrations between 10 and 100 microM. NSAIDs such as indomethacin, diclofenac and piroxicam and the glucocorticoids dexamethasone and hydrocortisone showed little or no activity. The histamine H1 antagonists mepyramine and ketotifen and the calcium antagonists verapamil, nifedipine and TMB-8 were also ineffective in suppressing FMLP-induced elastase release. Reduction in elastase release by azelastine, that accumulates in lung tissue during long-term treatment in animals, may contribute to its anti-inflammatory and anti-allergic effects which are thought to be central to its use in asthma therapy.
在本研究中，体外研究了具有不同作用方式的药物对FMLP刺激的人白细胞弹性蛋白酶释放的影响。将抗哮喘和抗过敏药物与知名的抗炎和抗组胺药物进行了比较。抗哮喘/抗过敏化合物氮卓斯汀、阿司咪唑和奥沙米特，以及5-脂氧合酶抑制剂NDGA，能够在10至100微摩尔的浓度范围内抑制人白细胞弹性蛋白酶的释放。非甾体抗炎药如吲哚美辛、双氯芬酸和吡罗昔康，以及糖皮质激素地塞米松和氢化可的松几乎没有或没有活性。组胺H1拮抗剂美吡拉敏和酮替芬，以及钙拮抗剂维拉帕米、硝苯地平和TMB-8在抑制FMLP诱导的弹性蛋白酶释放方面也无效。在动物长期治疗期间积聚在肺组织中的氮卓斯汀减少弹性蛋白酶释放，可能有助于其抗炎和抗过敏作用，这些作用被认为是其在哮喘治疗中应用的核心。
