504 Topical adenosine treatment inhibits inflammation and mucus production in viral acute rhinosinusitis

Abstract

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.