ObjectiveViral acute rhinosinusitis (ARS) is the leading cause of work and school absence and antibiotic over‐prescription. 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‐nasal tract. Here, we assessed the therapeutic potential of topical adenosine in a mouse model of viral ARS.MethodsThe 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‐only infection. We also investigated the inflammatory effect of both endogenous and exogenous adenosine in the sino‐nasal tract.ResultsTopical adenosine significantly inhibited the expression of pro‐inflammatory 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 A2A 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‐nasal tract. Instead, exogenous adenosine inhibited the baseline expression of TNF and IL‐1β in the nose. Additionally, baseline expression of ARs was lower in the nose than that in the trachea and lungs.ConclusionWe demonstrated that intranasal adenosine administration effectively decreased inflammation and mucus production in a mouse model of viral ARS.Level of EvidenceN/A Laryngoscope, 133:2095–2103, 2023

OBJECTIVES/GOALS: Viral acute rhinosinusitis (ARS), a.k.a, the common cold, affects millions every year. The symptoms caused by viral ARS dramatically affect the general well-being and functional levels of patients, causing work and school absence, and antibiotic abuse. In this study, we examined the therapeutic potential of topical adenosine in viral ARS METHODS/STUDY POPULATION: Rhinosinusitis was induced in WT and adenosine receptor (AR) knockout mice by respiratory syncytial virus (RSV) infection in the upper airways. Mice were subjected to adenosine or vehicle control within the sinuses. Adenosine receptor expression, inflammatory cytokine expression, and histologic mucus and inflammation score was assessed. The effect of endogenous adenosine accumulation within the sino-nasal tract was assessed in adenosine deaminase knockout (ADA-/-) mice. RESULTS/ANTICIPATED RESULTS: Topical administration of adenosine significantly inhibited the expression of pro-inflammatory cytokines, mucus production, and cell damage in the nose of mice with viral ARS, without prolonging virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). We also examined and compared the expression of ARs in the nasal tissue, trachea, and lungs. The nasal tissue exhibited the lowest baseline expression of ARs as compared to the lung and trachea which was further downregulated following adenosine treatment. Additionally, accumulation of endogenous adenosine in ADA-/- mice showed no signs of inflammation within the nasal tissue. Together, we demonstrated that topical adenosine effectively decreased inflammation and mucus production in a mouse model of viral ARS. DISCUSSION/SIGNIFICANCE: Previously, we found that topical adenosine dramatically enhances mucociliary clearance in the nose and sinuses. In this study, we found that nasal topical adenosine effectively decreased inflammation and mucus production in viral ARS. Our data suggest that nasal topical adenosine is an effective topical therapeutic option for viral ARS.