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The difference between targeting IL\u20105 or the IL\u20105 receptor, \u03b1 subunit (IL\u20105R\u03b1) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti\u2010IL\u20105R\u03b1 benralizumab and the anti\u2010IL\u20105 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Passively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine. The secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Benralizumab and mepolizumab significantly inhibited the AHR to histamine (maximal effect \u2212134.14 \u00b1 14.93% and \u2212108.29 \u00b1 32.16%, respectively), with benralizumab being 0.73 \u00b1 0.10 logarithm significantly more potent than mepolizumab. Benralizumab and mepolizumab significantly inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45 \u00b1 0.16 logarithm significantly more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated with increased levels of cAMP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Targeting the IL\u20105\/IL\u20105R\u03b1 axis is an effective strategy to prevent the AHR. Benralizumab was more potent than the mepolizumab and the concentration\u2010dependent beneficial effects of both these monoclonal antibodies were related to improved levels of cAMP in hyperresponsive airways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15240","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T20:43:55Z","timestamp":1598647435000},"page":"4750-4765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Targeting IL\u20105 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"Luigino","family":"Calzetta","sequence":"first","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice Ludovica","family":"Ritondo","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-9235","authenticated-orcid":false,"given":"Maria Gabriella","family":"Matera","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology, Department of Experimental Medicine University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Facciolo","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-5040","authenticated-orcid":false,"given":"Paola","family":"Rogliani","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01359-2015"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14751"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00135"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.121529"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.05.019"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01243.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2012.05.002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31324-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2016.04.022"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.03.011"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0770-7"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0306OC"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0386-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2015.11.004"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01165.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MR1117-426R"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00380.2003"},{"key":"e_1_2_10_20_1","unstructured":"European Medicines Agency. 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