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

Hyperinflammatory responses including the production of NLRP3-dependent interleukin (IL)-1 beta 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-1 beta in modulating IAV disease in vivo is currently not well defined. Here, we identified that activation of NLRP3-dependent IL-1 beta responses occurs rapidly following HKx31 H3N2 infection, prior to the onset of severe IAV disease. Mature IL-1 beta was detectable in vivo in both hemopoietic and nonhemopoietic cells. Significantly, therapeutic inhibition of IL-1 beta in the airways with intranasal anti-IL-1 beta 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-1 beta from day 1 postinfection also improved survival. Together, these studies specifically define a role for IL-1 beta in contributing to the development of hyperinflammation and disease and indicate that targeting IL-1 beta is a potential therapeutic strategy for severe IAV infections.

Automated summary

In severe influenza A virus infections, early therapeutic targeting of IL-1 beta can significantly prolong survival and reduce airway inflammation, demonstrating its crucial role in hyperinflammation and disease development.