tetano
Editor, Senior Moderator
Immunol Cell Biol
. 2021 Apr 9.
doi: 10.1111/imcb.12459. Online ahead of print.
IL-1? exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection
Abdullah Bawazeer[SUP] 1 2 [/SUP], Sarah Rosli[SUP] 1 2 [/SUP], Christopher M Harpur[SUP] 1 2 [/SUP], Callum Ah Docherty[SUP] 1 2 [/SUP], Ashley Mansell[SUP] 1 2 [/SUP], Michelle D Tate[SUP] 1 2 [/SUP]
Affiliations
Abstract
Hyperinflammatory responses including the production of NLRP3-dependent IL-1? 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? in modulating IAV disease in vivo is currently not well defined. Here, we identified that activation of NLRP3-dependent IL-1? responses occurs rapidly following HKx31 H3N2 infection, prior to the onset of severe IAV disease. Mature IL-1? was detectible in vivo in both haemopoietic and non-haemopoietic cells. Significantly, therapeutic inhibition of IL-1? in the airways with intranasal anti-IL-1? antibody treatment from day three post-infection, corresponding to the onset of clinical signs of disease, significantly prolonged survival and reduced inflammation in the airways. Importantly, early targeting of IL-1? from day 1 post-infection also improved survival. Together, these studies specifically define a role for IL-1? in contributing to the development of hyperinflammation and disease and indicates targeting IL-1? is a potential therapeutic strategy for severe IAV infections.
Keywords: IL-1?; Influenza A virus; disease; inflammation.
. 2021 Apr 9.
doi: 10.1111/imcb.12459. Online ahead of print.
IL-1? exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection
Abdullah Bawazeer[SUP] 1 2 [/SUP], Sarah Rosli[SUP] 1 2 [/SUP], Christopher M Harpur[SUP] 1 2 [/SUP], Callum Ah Docherty[SUP] 1 2 [/SUP], Ashley Mansell[SUP] 1 2 [/SUP], Michelle D Tate[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33834544
- DOI: 10.1111/imcb.12459
Abstract
Hyperinflammatory responses including the production of NLRP3-dependent IL-1? 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? in modulating IAV disease in vivo is currently not well defined. Here, we identified that activation of NLRP3-dependent IL-1? responses occurs rapidly following HKx31 H3N2 infection, prior to the onset of severe IAV disease. Mature IL-1? was detectible in vivo in both haemopoietic and non-haemopoietic cells. Significantly, therapeutic inhibition of IL-1? in the airways with intranasal anti-IL-1? antibody treatment from day three post-infection, corresponding to the onset of clinical signs of disease, significantly prolonged survival and reduced inflammation in the airways. Importantly, early targeting of IL-1? from day 1 post-infection also improved survival. Together, these studies specifically define a role for IL-1? in contributing to the development of hyperinflammation and disease and indicates targeting IL-1? is a potential therapeutic strategy for severe IAV infections.
Keywords: IL-1?; Influenza A virus; disease; inflammation.