Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation

Kristi J. Warren, Jill A. Poole, Jenea M. Sweeter, Jane M. DeVasure, John D. Dickinson, R. Stokes Peebles, Todd A. Wyatt

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.

Original languageEnglish (US)
Article number206
JournalRespiratory Research
Issue number1
StatePublished - Dec 2021


  • Group 2 innate lymphoid cells (ILC2)
  • Group 3 innate lymphoid cells (ILC3)
  • Interleukin-23 (IL-23)
  • Interleukin-33 (IL-33)
  • Respiratory syncytial virus-A2 (RSV-A2)
  • Thymic stromal lymphopoietin (TSLP)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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