Inhibition of uric acid or IL‐1β ameliorates respiratory syncytial virus immunopathology and development of asthma

Abstract

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‐1β in RSV immunopathology and asthma predisposition. Methods Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro‐IL‐1β 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‐1β mRNA and protein. Inhibition of UA or IL‐1β 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‐1β 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‐1β 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.

Advances and recent developments in asthma in 2020

“…Schuler et al show that uric acid and IL-1β play a role in the mechanism, and their inhibition can prevent the development of asthma after neonatal RSV infection, thus being a possible therapeutic target. 74 A prospective study suggested infants suffering from bronchiolitis at less than 6 months of age have a twice higher risk of doctor-diagnosed asthma after follow-up for 11-13 years compared to general Finnish population and that the RSV was the main reason for bronchiolitis in these infants. 75 The EAACI Influenza in Asthma Task Force performed a scoping review about the influenza burden, prevention, and treatment in asthma.…”

Association of Serum Uric Acid Levels with COVID-19 Severity

“…Conversely, SUA levels are increased in infections of other systems. Respiratory syncytial virus (RSV) induces increased UA levels in mouse neonates, and the inhibition of UA by xanthine oxidase inhibitor decreases mucus production, reduces cellular in ltrates to the lungs (particularly ILC2s), and decreases type 2 immune responses [8]. UA is a biomarker of early cystic brosis lung disease [22], and high SUA is positively correlated with severe infections such as sepsis [23].…”

Association of serum uric acid levels with COVID-19 severity

“…Respiratory syncytial virus (RSV) induces increased UA levels in mouse neonates, and the inhibition of UA by xanthine oxidase inhibitor decreases mucus production, reduces cellular in ltrates to the lungs (particularly ILC2s), and decreases type 2 immune responses [8]. UA is a biomarker of early cystic brosis lung disease [22], and high SUA is positively correlated with severe infections such as sepsis [23].…”

“…Some studies have investigated the relationship between SUA levels and in ammation (bacteria, viruses or autoimmunity), but the conclusions were inconsistent. Most studies had shown that in ammation could induce the increase of SUA, particularly when the virus invaded the respiratory system [8]. However, SUA tend to decrease during central nervous system infection [6,9].…”