IL-4Rα Blockade Reduces Influenza-Associated Morbidity in a Murine Model of Allergic Asthma

Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. The pathways responsible for this observation are unknown. Here, we used a murine model of allergic asthma and determined whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of Th2 signalling, improved outcomes. Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p<.05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.Funding: Supported by the Canadian Institutes of Health Research (CIHR).Declaration of Interest: The authors have declared that no conflict of interest exists.Ethical Approval: Mice were housed in a specific pathogen-free environment with protocols approved by the Animal Care and Biosafety Committees of the University of British Columbia.