Effect of IL-1β and TNF-αvs IL-13 on bronchial hyperresponsiveness, β2-adrenergic responses and cellularity of bronchial alveolar lavage fluid

M. Horiba, N. Qutna, P. Gendapodi, S. Agrawal, K. Sapkota, P. Abel, R. G. Townley
{"title":"Effect of IL-1β and TNF-αvs IL-13 on bronchial hyperresponsiveness, β2-adrenergic responses and cellularity of bronchial alveolar lavage fluid","authors":"M. Horiba,&nbsp;N. Qutna,&nbsp;P. Gendapodi,&nbsp;S. Agrawal,&nbsp;K. Sapkota,&nbsp;P. Abel,&nbsp;R. G. Townley","doi":"10.1111/j.1474-8673.2011.00465.x","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p><b>1</b> Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β<sub>2</sub>-adrenoceptor agonism.</p>\n <p><b>2</b> Naïve or OVA-sensitized mice were treated for 3 days with IL-1β (250 U), TNF-α (150 ng), IL-13 (5 μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β<sub>2</sub>-adrenoceptor agonist, was assessed 24 h after the last cytokine administration.</p>\n <p><b>3</b> In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh.</p>\n <p><b>4</b> In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β.</p>\n <p><b>5</b> Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice.</p>\n <p><b>6</b> Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β<sub>2</sub>-adrenoceptor responsiveness.</p>\n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2011-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1474-8673.2011.00465.x","citationCount":"14","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1474-8673.2011.00465.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 14

Abstract

1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β2-adrenoceptor agonism.

2 Naïve or OVA-sensitized mice were treated for 3 days with IL-1β (250 U), TNF-α (150 ng), IL-13 (5 μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β2-adrenoceptor agonist, was assessed 24 h after the last cytokine administration.

3 In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh.

4 In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β.

5 Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice.

6 Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β2-adrenoceptor responsiveness.

IL-1β、TNF-αvs IL-13对支气管高反应性、β2-肾上腺素能反应及支气管肺泡灌洗液细胞结构的影响
1哮喘患者支气管灌洗液中IL-13、IL-1β和TNF-α水平升高,可诱导气道高反应性(AHR)等支气管哮喘的某些显著特征。在本研究中,我们研究了这些细胞因子在naïve小鼠和卵清蛋白(OVA)致敏小鼠中对甲胆碱(MCh)支气管收缩的影响以及β2-肾上腺素受体激动作用诱导的功能性拮抗作用。2只Naïve或ova致敏小鼠分别给予IL-1β (250 U)、TNF-α (150 ng)、IL-13 (5 μg)或IL-1β与TNF-α或IL-1β与IL-13联合治疗3天。在最后一次细胞因子给药24小时后,评估mch诱导的支气管收缩及其对β2-肾上腺素受体激动剂沙丁胺醇的敏感性。3在naïve小鼠中,IL-1β与TNF-α、单独使用IL-13或与IL-1β联合使用可显著提高MCh的应答性,而单独使用IL-1β或TNF-α则无此作用。在ova致敏小鼠中也得到了类似的结果,除了单独用IL-13治疗不会增加对MCh的敏感性。4在naïve小鼠中,只有IL-1β和TNF-α联合治疗才能显著降低沙丁胺醇的敏感性。在卵细胞致敏小鼠中,TNF-α、IL-13或IL-13联合IL-1β治疗可显著降低沙丁胺醇敏感性。在ova致敏小鼠中,除IL-13外,所有细胞因子及其组合均增加了炎症细胞内流。我们的数据不支持炎症细胞内流与AHR之间的联系。此外,il -13诱导AHR的机制可能与β2-肾上腺素受体反应性降低有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信