Necroptosis blockade prevents lung injury in severe influenza.
Nature
; 628(8009): 835-843, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38600381
ABSTRACT
Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Infecções por Orthomyxoviridae
/
Inibidores de Proteínas Quinases
/
Proteína Serina-Treonina Quinases de Interação com Receptores
/
Lesão Pulmonar
/
Necroptose
Idioma:
En
Revista:
Nature
/
Nature (Lond.)
/
Nature (London)
Ano de publicação:
2024
Tipo de documento:
Article