tetano
Editor, Senior Moderator
EBioMedicine
. 2022 Oct 6;85:104299.
doi: 10.1016/j.ebiom.2022.104299. Online ahead of print.
Interleukin-1 and the NLRP3 inflammasome in COVID-19: Pathogenetic and therapeutic implications
Nicola Potere[SUP] 1 [/SUP], Marco Giuseppe Del Buono[SUP] 2 [/SUP], Roberto Caricchio[SUP] 3 [/SUP], Paul C Cremer[SUP] 4 [/SUP], Alessandra Vecchié[SUP] 5 [/SUP], Ettore Porreca[SUP] 1 [/SUP], Daniela Dalla Gasperina[SUP] 6 [/SUP], Francesco Dentali[SUP] 6 [/SUP], Antonio Abbate[SUP] 7 [/SUP], Aldo Bonaventura[SUP] 8 [/SUP]
Affiliations
Abstract
A hyperinflammatory response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection crucially worsens clinical evolution of coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) triggers the activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Enhanced inflammasome activity has been associated with increased disease severity and poor prognosis. Evidence suggests that inflammasome activation and interleukin-1β (IL-1β) release aggravate pulmonary injury and induce hypercoagulability, favoring progression to respiratory failure and widespread thrombosis eventually leading to multiorgan failure and death. Observational studies with the IL-1 blockers anakinra and canakinumab provided promising results. In the SAVE-MORE trial, early treatment with anakinra significantly shortened hospital stay and improved survival in patients with moderate-to-severe COVID-19. In this review, we summarize current evidence supporting the pathogenetic role of the NLRP3 inflammasome and IL-1β in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19.
Keywords: Anakinra; C-reactive protein; COVID-19; Canakinumab; Colchicine; IL-18; IL-1β; NLRP3 inflammasome; SARS-CoV-2.
. 2022 Oct 6;85:104299.
doi: 10.1016/j.ebiom.2022.104299. Online ahead of print.
Interleukin-1 and the NLRP3 inflammasome in COVID-19: Pathogenetic and therapeutic implications
Nicola Potere[SUP] 1 [/SUP], Marco Giuseppe Del Buono[SUP] 2 [/SUP], Roberto Caricchio[SUP] 3 [/SUP], Paul C Cremer[SUP] 4 [/SUP], Alessandra Vecchié[SUP] 5 [/SUP], Ettore Porreca[SUP] 1 [/SUP], Daniela Dalla Gasperina[SUP] 6 [/SUP], Francesco Dentali[SUP] 6 [/SUP], Antonio Abbate[SUP] 7 [/SUP], Aldo Bonaventura[SUP] 8 [/SUP]
Affiliations
- PMID: 36209522
- DOI: 10.1016/j.ebiom.2022.104299
Abstract
A hyperinflammatory response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection crucially worsens clinical evolution of coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) triggers the activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Enhanced inflammasome activity has been associated with increased disease severity and poor prognosis. Evidence suggests that inflammasome activation and interleukin-1β (IL-1β) release aggravate pulmonary injury and induce hypercoagulability, favoring progression to respiratory failure and widespread thrombosis eventually leading to multiorgan failure and death. Observational studies with the IL-1 blockers anakinra and canakinumab provided promising results. In the SAVE-MORE trial, early treatment with anakinra significantly shortened hospital stay and improved survival in patients with moderate-to-severe COVID-19. In this review, we summarize current evidence supporting the pathogenetic role of the NLRP3 inflammasome and IL-1β in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19.
Keywords: Anakinra; C-reactive protein; COVID-19; Canakinumab; Colchicine; IL-18; IL-1β; NLRP3 inflammasome; SARS-CoV-2.