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局部用氮卓斯汀可降低鼻上皮细胞上嗜酸性粒细胞的活化及细胞间黏附分子-1的表达:一种抗过敏活性。

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity.

作者信息

Ciprandi G, Pronzato C, Passalacqua G, Ricca V, Grögen J, Mela G S, Varese P, Bertolini C, Bagnasco M, Canonica G W

机构信息

Department of Internal Medicine, Genoa University, Italy.

出版信息

J Allergy Clin Immunol. 1996 Dec;98(6 Pt 1):1088-96. doi: 10.1016/s0091-6749(96)80196-5.

Abstract

BACKGROUND

It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray).

OBJECTIVE

The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction.

METHODS

The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental).

RESULTS

Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Koch's split-plot statistical analysis.

CONCLUSION

Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

摘要

背景

众所周知,变应原特异性鼻激发试验(ASNC)是评估药物抗变态反应活性的有效工具。氮卓斯汀是一种新型抗组胺药,也有局部用剂型(即鼻喷雾剂)。

目的

本研究旨在评估氮卓斯汀鼻喷雾剂对ASNC后早期反应和晚期反应中炎症变化的影响。

方法

本研究采用双盲、安慰剂对照、随机平行组设计。在花粉季节之外招募了20例花粉过敏患者。在基线期(T0)和洗脱1周后(T7)进行ASNC。在T7时,10例患者向鼻孔喷入氮卓斯汀(1喷),10例患者使用安慰剂。30分钟后进行ASNC。所考虑的参数(在早期和晚期反应期间评估)为:(1)临床体征和症状,(2)细胞学评估(中性粒细胞和嗜酸性粒细胞),(3)介质测定(嗜酸性粒细胞阳离子蛋白和髓过氧化物酶),以及(4)鼻上皮细胞上细胞间黏附分子-1(ICAM-1)的表达。我们将注意力集中在ICAM-1上,因为它是嗜酸性粒细胞上表达的白细胞功能相关抗原-1和Mac-1的天然配体。此外,ICAM-1仅在变应原暴露时(天然和实验性)在上皮细胞上表达。

结果

安慰剂对所考虑的参数没有任何影响。给予氮卓斯汀后,在早期和晚期反应期间均观察到总症状评分、嗜酸性粒细胞和中性粒细胞浸润以及ICAM-1表达显著降低。此外,晚期反应期间血清嗜酸性粒细胞阳离子蛋白水平降低,而髓过氧化物酶不受治疗影响。这些发现通过强大的科赫裂区统计分析得到证实。

结论

氮卓斯汀具有抗变态反应活性,主要影响嗜酸性粒细胞功能并下调鼻上皮细胞上ICAM-1的表达。

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