Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma
Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma
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DOI：
10.1067/mai.2000.104552
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发表时间：
2000-03-01
影响因子：
14.2
通讯作者：
Peden, DB
中科院分区：
文献类型：
--
作者：
Eldridge, MW;Peden, DB
背景：最近的流行病学和体内研究表明，吸入性内毒素在哮喘发病中起着重要作用。目的：本研究旨在探讨过敏性哮喘患者鼻变应原激发对随后的内毒素激发的影响。方法：采用双鼻随机交叉设计，对12例哮喘患者的个体鼻孔进行激发和冲洗，其中一个鼻孔在基线鼻腔冲洗后立即接受生理盐水，另一个鼻孔接受尘螨抗原，4小时后两个鼻孔均暴露于生理盐水或内毒素。粉尘螨抗原(粉尘螨)和内毒素(Escherichia Roll026：B6)剂量分别为100AU和1000 ng。分别在最初激发后8小时和24小时进行激发后灌洗。然后，受试者在至少3周后返回，以便交叉到研究臂。检测鼻腔灌洗液中细胞总数和分类计数、IL-8、IL-6、细胞间黏附分子-1、GM-CSF、嗜酸性粒细胞阳离子蛋白、髓过氧化物酶和可溶性CD14。结果：与生理盐水和生理盐水/内毒素暴露组相比，尘螨/内毒素暴露组大鼠鼻腔灌洗液中炎症细胞总数在暴露后8h显著增加。不同的细胞计数显示，尘螨/内毒素暴露8小时后出现类似的中性粒细胞和嗜酸性炎症。结论：这些数据表明哮喘患者的过敏原和内毒素暴露之间存在相互作用，表明先前的过敏原攻击显著增强了内毒素诱导的炎症。此外，这些数据提供了进一步的证据，表明伴随的过敏原和内毒素暴露可能是哮喘发病的一个重要因素。
Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis.Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma.Methods: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows, Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen, Four hours later both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia roll 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14.Results: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours.Conclusions: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may he an important factor in asthma pathogenesis.