Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis.
Elife
; 92020 03 02.
Article
en En
| MEDLINE
| ID: mdl-32118580
ABSTRACT
Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature with increased IL-18, IL-1ß, caspase-1 activity and ASC speck release (Scambler et al. eLife 2019). Here we show that CFTR modulators down regulate this exaggerated proinflammatory response following LPS/ATP stimulation. In vitro application of ivacaftor/lumacaftor or ivacaftor/tezacaftor to CF monocytes showed a significant reduction in IL-18, whereas IL-1ß was only reduced with ivacaftor/tezacaftor. Thirteen adults starting ivacaftor/lumacaftor and eight starting ivacaftor/tezacaftor were assessed over three months. Serum IL-18 and TNF decreased significantly with treatments, but IL-1ß only declined following ivacaftor/tezacaftor. In (LPS/ATP-stimulated) PBMCs, IL-18/TNF/caspase-1 were all significantly decreased and IL-10 was increased with both combinations. Ivacaftor/tezacaftor alone showed a significant reduction in IL-1ß and pro-IL-1ß mRNA. This study demonstrates that these CFTR modulator combinations have potent anti-inflammatory properties, in addition to their ability to stimulate CFTR function, which could contribute to improved clinical outcomes.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinolonas
/
Regulador de Conductancia de Transmembrana de Fibrosis Quística
/
Fibrosis Quística
/
Benzodioxoles
/
Aminofenoles
/
Aminopiridinas
/
Indoles
/
Inflamación
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido