tetano
Editor, Senior Moderator
J Clin Transl Res
. 2021 Jan 27;7(1):116-120.
Interleukin-13 as a target to alleviate severe coronavirus disease 2019 and restore lung homeostasis
Lachlan Paul Deimel[SUP] 1 [/SUP], Zheyi Li[SUP] 1 [/SUP], Charani Ranasinghe[SUP] 1 [/SUP]
Affiliations
Abstract
The ongoing coronavirus disease (COVID-19) pandemic urgently requires the availability of interventions that improve outcomes for those with severe disease. Since severe acute respiratory syndrome coronavirus 2 infection is characterized by dysregulated lung mucosae, and that mucosal homeostasis is heavily influenced by interleukin (IL)-13 activity, we explore recent findings indicating that IL-13 production is proportional to disease severity. We propose that excessive IL-13 contributes to the progression of severe/fatal COVID-19 by (1) promoting the recruitment of immune cells that express inflammatory cytokines, causing a cytokine storm that results in widespread destruction of lung tissue, (2) directly facilitating tissue-remodeling that causes airway hyperinflammation and obstruction, and (3) diverting the immune system away from developing high-quality cytotoxic T cells that confer effective anti-viral immunity. These factors may cumulatively result in significant lung distress, multi-organ failure, and death. Here, we suggest repurposing existing IL-13-inhibiting interventions, including antibody therapies routinely used for allergic lung hyperinflammation, as well as viral vector-based approaches, to alleviate disease. Since many of these strategies have previously been shown to be both safe and effective, this could prove to be a highly cost-effective solution.
Relevance for patients: There remains a desperate need to establish medical interventions that reliably improves outcomes for patients suffering from COVID-19. We explore the role of IL-13 in maintaining homeostasis at the lung mucosae and propose that its dysregulation during viral infection may propagate the hallmarks of severe disease - further exploration may provide a platform for invaluable therapeutics.
Keywords: IL-13Ra2; ILC2; coronavirus disease-19; cytokine storm; inflammation; interleukin-13; interleukin-4/interleukin-13 antagonists; lung mucosae; severe acute respiratory syndrome coronavirus 2.
. 2021 Jan 27;7(1):116-120.
Interleukin-13 as a target to alleviate severe coronavirus disease 2019 and restore lung homeostasis
Lachlan Paul Deimel[SUP] 1 [/SUP], Zheyi Li[SUP] 1 [/SUP], Charani Ranasinghe[SUP] 1 [/SUP]
Affiliations
- PMID: 34027204
- PMCID: PMC8132187
Abstract
The ongoing coronavirus disease (COVID-19) pandemic urgently requires the availability of interventions that improve outcomes for those with severe disease. Since severe acute respiratory syndrome coronavirus 2 infection is characterized by dysregulated lung mucosae, and that mucosal homeostasis is heavily influenced by interleukin (IL)-13 activity, we explore recent findings indicating that IL-13 production is proportional to disease severity. We propose that excessive IL-13 contributes to the progression of severe/fatal COVID-19 by (1) promoting the recruitment of immune cells that express inflammatory cytokines, causing a cytokine storm that results in widespread destruction of lung tissue, (2) directly facilitating tissue-remodeling that causes airway hyperinflammation and obstruction, and (3) diverting the immune system away from developing high-quality cytotoxic T cells that confer effective anti-viral immunity. These factors may cumulatively result in significant lung distress, multi-organ failure, and death. Here, we suggest repurposing existing IL-13-inhibiting interventions, including antibody therapies routinely used for allergic lung hyperinflammation, as well as viral vector-based approaches, to alleviate disease. Since many of these strategies have previously been shown to be both safe and effective, this could prove to be a highly cost-effective solution.
Relevance for patients: There remains a desperate need to establish medical interventions that reliably improves outcomes for patients suffering from COVID-19. We explore the role of IL-13 in maintaining homeostasis at the lung mucosae and propose that its dysregulation during viral infection may propagate the hallmarks of severe disease - further exploration may provide a platform for invaluable therapeutics.
Keywords: IL-13Ra2; ILC2; coronavirus disease-19; cytokine storm; inflammation; interleukin-13; interleukin-4/interleukin-13 antagonists; lung mucosae; severe acute respiratory syndrome coronavirus 2.