IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma.

Autor: Shahangian K; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Ngan DA; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Chen HHR; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Oh Y; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Tam A; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Wen J; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Cheung C; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Knight DA; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia., Dorscheid DR; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Hackett TL; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Hughes MR; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada., McNagny KM; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada., Hirota JA; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada., Niikura M; Department of Health Sciences, Simon Fraser University, Vancouver, BC, Canada., Man SFP; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Sin DD; Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Room 166, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada. don.sin@hli.ubc.ca.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada. don.sin@hli.ubc.ca.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2021 Mar 02; Vol. 22 (1), pp. 75. Date of Electronic Publication: 2021 Mar 02.
DOI: 10.1186/s12931-021-01669-0
Abstrakt: Background: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma 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 T h 2 signalling, improved their outcomes.
Methods: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy.
Results: 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.
Conclusion: 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.
Databáze: MEDLINE
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