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There are limited treatment options available to ameliorate the symptoms caused by viral ARS. We have previously demonstrated that topical adenosine treatment enhances mucociliary clearance in the sino\u2010nasal tract. Here, we assessed the therapeutic potential of topical adenosine in a mouse model of viral ARS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effect of topical adenosine on inflammatory response and mucin gene expression was examined in a mouse model of viral ARS induced by respiratory syncytial virus (RSV) nasal\u2010only infection. We also investigated the inflammatory effect of both endogenous and exogenous adenosine in the sino\u2010nasal tract.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Topical adenosine significantly inhibited the expression of pro\u2010inflammatory cytokines, goblet hyperplasia, mucin expression, and cell damage in the nose of mice with viral ARS. This treatment did not prolong virus clearance. This inhibitory effect was primarily mediated by the A<jats:sub>2A<\/jats:sub> adenosine receptor (AR). Although previous studies have shown that adenosine induces a robust inflammatory response in the lungs, neither endogenous nor exogenous adenosine produced inflammation in the sino\u2010nasal tract. Instead, exogenous adenosine inhibited the baseline expression of TNF and IL\u20101\u03b2 in the nose. Additionally, baseline expression of ARs was lower in the nose than that in the trachea and lungs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated that intranasal adenosine administration effectively decreased inflammation and mucus production in a mouse model of viral ARS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>N\/A <jats:italic>Laryngoscope<\/jats:italic>, 133:2095\u20132103, 2023<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30541","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T11:40:07Z","timestamp":1672227607000},"page":"2095-2103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Topical Adenosine Inhibits Inflammation and Mucus Production in Viral Acute 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tilley","sequence":"additional","affiliation":[{"name":"Department of Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-7712","authenticated-orcid":false,"given":"Xiaoyang","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1289","article-title":"Common cold","volume":"57","author":"Worrall G","year":"2011","journal-title":"Can Fam 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