Journal
ALLERGY
Volume 75, Issue 9, Pages 2279-2293Publisher
WILEY
DOI: 10.1111/all.14310
Keywords
allopurinol; asthma; interleukin-1 beta; respiratory syncytial virus; uric acid
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Funding
- Mary H. Weiser Food Allergy Center
- National Institute of Allergy and Infectious Diseases [PO1AI1089473, RO1AI138348]
- National Heart, Lung, and Blood Institute [5T32HL007517-30]
- NIH [PO1AI1089473, 5T32HL007517-30, AI138348]
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Background Respiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown. Objective To investigate the role of uric acid (UA) and IL-1 beta in RSV immunopathology and asthma predisposition. Methods Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro-IL-1 beta mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6-7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL-1 receptor antagonist was administered during RSV infection. Results Human tracheal aspirates from RSV-infected infants showed elevated pro-IL-1 beta mRNA and protein. Inhibition of UA or IL-1 beta during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL-1 beta during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen. Conclusions Inhibiting UA and IL-1 beta during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen-induced asthma, and presents new therapeutic targets to reduce early-life viral-induced asthma development.
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