吸入性糖皮质激素与抗白三烯药物对哮喘儿童淋巴细胞P-糖蛋白（PGP）表达的抗炎作用比较

The anti-inflammatory effects of inhaled corticosteroids versus anti-leukotrienes on the lymphocyte P-glycoprotein (PGP) expression in asthmatic children.

作者信息

Kopriva Frantisek, Dzubak Petr, Potesil Jan, Hajduch Marian

机构信息

Medical Faculty, Pediatrics, Olomouc, Czech Republic.

出版信息

J Asthma. 2009 May;46(4):366-70. doi: 10.1080/02770900902777767.

DOI:10.1080/02770900902777767

PMID:19484671

Abstract

BACKGROUND

Inhaled corticosteroids (ICS) are used in asthma therapy for their anti-inflammatory effects. P-glycoprotein (PGP) is a transmembrane efflux pump for many drugs, including corticosteroids. Expression of PGP is associated with therapy resistant disease.

OBJECTIVE

The purpose of this study was to compare expression levels of PGP in blood lymphocytes of pediatric asthma patients either on ICS or on the leukotriene inhibitor montelukast medication.

PATIENTS AND METHODS

The evaluation of lymphocyte PGP expression was performed on a sample of 99 children (66 boys and 33 girls) aged 2-18 (median 12) years with intermittent or persisting mild asthma, (as defined by GINY 2002). The asthmatic children were divided into 3 groups: (1) treated by ICS budesonide 200-400 microg per day (n = 27) more than 1 year; (2) treated by oral montelukast 4 or 5 mg at an age-based dose (n = 16); and (3) treated by inhaled corticosteroids and montelukast (n = 45). Reference PGP values were obtained from a group of 64 healthy children (23 boys and 29 girls) aged 2-15 years (median, 10 years). The expression of lymphocyte PGP was determined on fixed and permeabilized blood mononuclear cells using indirect immunofluorescence staining technique by flow cytometry modified according to Boer et al., 1997.

RESULTS

Based on the weighted medians for PGP expression in peripheral blood lymphocytes, we found a significant difference (p < 10(-3)) between the group of asthma patients (n = 99), (619 +/- 5.3) and healthy controls (n = 64) (446.9 +/- 4.4). Second, there was a lower level of PGP expression in the group treated by ICS (548.6 +/- 9) than the group treated by montelukast and montelukast with budesonide (643.2 +/- 6.3) (p < 10(-6)).

CONCLUSIONS

The anti-inflammatory activity of ICS is more effective in decreasing the production of pro-inflammatory mediators and results in reduced multidrug resistence (MDR-1) gene activity and expression of lymphocyte PGP in asthmatic children.

摘要

背景

吸入性糖皮质激素（ICS）因其抗炎作用而用于哮喘治疗。P-糖蛋白（PGP）是一种跨膜外排泵，可转运包括糖皮质激素在内的多种药物。PGP的表达与治疗抵抗性疾病相关。

目的

本研究旨在比较接受ICS或白三烯抑制剂孟鲁司特治疗的小儿哮喘患者血淋巴细胞中PGP的表达水平。

患者和方法

对99名年龄在2至18岁（中位数12岁）的间歇性或持续性轻度哮喘儿童（按照2002年GINY标准定义）进行淋巴细胞PGP表达评估。哮喘儿童分为3组：（1）每天接受200 - 400微克布地奈德ICS治疗超过1年（n = 27）；（2）按年龄剂量口服4或5毫克孟鲁司特治疗（n = 16）；（3）接受吸入性糖皮质激素和孟鲁司特联合治疗（n = 45）。从64名年龄在2至15岁（中位数10岁）的健康儿童（23名男孩和29名女孩）中获取PGP参考值。采用间接免疫荧光染色技术，通过根据Boer等人1997年方法改进的流式细胞术，在固定并透化处理的血液单核细胞上测定淋巴细胞PGP的表达。

结果

基于外周血淋巴细胞中PGP表达的加权中位数，我们发现哮喘患者组（n = 99）（619±5.3）与健康对照组（n = 64）（446.9±4.4）之间存在显著差异（p < 10⁻³）。其次，接受ICS治疗组（548.6±9）的PGP表达水平低于接受孟鲁司特以及孟鲁司特与布地奈德联合治疗组（643.2±6.3）（p < 10⁻⁶）。