Interleukin-1β exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection

Abdulah O.S. Bawazeer, Sarah Rosli, Christopher M. Harpur, Callum A.H. Docherty, Ashley Mansell, Michelle D. Tate

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)


Hyperinflammatory responses including the production of NLRP3-dependent interleukin (IL)-1β is a characteristic feature of severe and fatal influenza A virus (IAV) infections. The NLRP3 inflammasome has been shown to play a temporal role during severe IAV immune responses, with early protective and later detrimental responses. However, the specific contribution of IL-1β in modulating IAV disease in vivo is currently not well defined. Here, we identified that activation of NLRP3-dependent IL-1β responses occurs rapidly following HKx31 H3N2 infection, prior to the onset of severe IAV disease. Mature IL-1β was detectable in vivo in both hemopoietic and nonhemopoietic cells. Significantly, therapeutic inhibition of IL-1β in the airways with intranasal anti-IL-1β antibody treatment from day 3 postinfection, corresponding to the onset of clinical signs of disease, significantly prolonged survival and reduced inflammation in the airways. Importantly, early targeting of IL-1β from day 1 postinfection also improved survival. Together, these studies specifically define a role for IL-1β in contributing to the development of hyperinflammation and disease and indicate that targeting IL-1β is a potential therapeutic strategy for severe IAV infections.

Original languageEnglish
Pages (from-to)737-748
Number of pages12
JournalImmunology and Cell Biology
Issue number7
Publication statusPublished - Aug 2021


  • Disease
  • IL-1β
  • inflammation
  • influenza A virus

Cite this