Ventura M T, Giuliano G, Di Corato R, Tursi A
Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Italy.
Immunopharmacol Immunotoxicol. 1998 Aug;20(3):383-98. doi: 10.3109/08923979809034821.
In this paper, the effect of azelastine hydrochloride, a potent inhibitor of leukotrienes (LTs) and H1 receptors for histamine, was assessed as regards modulation of in vitro eosinophilic chemotaxis. In this respect, chemotaxis of eosinophils (EOS), isolated from the peripheral blood of untreated allergic subjects in the acute phase, was significantly diminished after in vitro treatment with azelastine in comparison to values before treatment. When EOS were pre-incubated with serial dilutions of the drug, it was observed that azelastine inhibited chemotaxis in a dose-dependent fashion. Since azelastine acts in vitro as a regulator of the calcium pump, EOS were pre-incubated with different concentrations (0.6 and 3.0 mM) of Ca++. In these experimental conditions azelastine was able to reduce EOS chemotactic activity only in the presence of 0.6 mM Ca++, whereas with higher Ca++ concentrations (3.0 mM) the inhibitory effect of the drug was abrogated. On the other hand, particular attention was paid to inhaled budesonide, a non halogenated glucocorticosteroid derivative, structurally related to 16 alpha-hydroxy prednisolone, which represents a helpful for treatment mild to moderate asthma. Data obtained after in vitro treatment with budesonide of a group of allergic patients demonstrated that EOS chemotactic activity was significantly reduced in these subjects. Conclusively our data show that 1) azelastine acts as a dose-dependent antagonist of chemotaxis; 2) it may exert this action by inhibiting Ca++ flow into cells; 3) inhaled budesonide may induce inhibition of bronchial inflammation by downregulating EOS chemotactic capacity.
本文评估了盐酸氮卓斯汀（一种白三烯（LTs）和组胺H1受体的强效抑制剂）对体外嗜酸性粒细胞趋化性的调节作用。在这方面，与治疗前的值相比，用氮卓斯汀体外处理后，从急性期未经治疗的过敏受试者外周血中分离出的嗜酸性粒细胞（EOS）的趋化性显著降低。当EOS与该药物的系列稀释液预孵育时，观察到氮卓斯汀以剂量依赖性方式抑制趋化性。由于氮卓斯汀在体外作为钙泵的调节剂起作用，EOS与不同浓度（0.6和3.0 mM）的Ca++预孵育。在这些实验条件下，氮卓斯汀仅在存在0.6 mM Ca++时能够降低EOS趋化活性，而在较高的Ca++浓度（3.0 mM）下，该药物的抑制作用被消除。另一方面，特别关注了吸入用布地奈德，一种与16α-羟基泼尼松龙结构相关的非卤化糖皮质激素衍生物，它对治疗轻度至中度哮喘有帮助。一组过敏患者用布地奈德体外治疗后获得的数据表明，这些受试者的EOS趋化活性显著降低。总之，我们的数据表明：1）氮卓斯汀作为趋化性的剂量依赖性拮抗剂起作用；2）它可能通过抑制Ca++流入细胞发挥这种作用；3）吸入用布地奈德可能通过下调EOS趋化能力诱导支气管炎症的抑制。
