Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model

• Published in: Experimental lung research 2024, Vol.50 (1), p.118-126
• Main Authors: Hancock, David G, Berry, Luke, Scott, Naomi M, Mincham, Kyle T, Ditcham, William, Larcombe, Alexander N, Clements, Barry
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; Animals; Bronchoalveolar Lavage Fluid; Cytokines - metabolism; Disease Models, Animal; Ethanol - administration & dosage; Ethanol - pharmacology; Female; Lung - drug effects; Lung - virology; Macrophages - drug effects; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections - drug therapy; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Viral Load - drug effects
• ISSN: 0190-2148; 1521-0499
• DOI: 10.1080/01902148.2024.2346320

Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 10 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.