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2 mars 2020
- doi: 10.7554/eLife.54556
- issn: 2050-084X
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info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.54556
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info:eu-repo/semantics/altIdentifier/pmid/32118580
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info:eu-repo/semantics/altIdentifier/eissn/2050-084X
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E0016C3B61204
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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CF (Disease) Pancreatic cystic fibrosis Fibrocystic disease of pancreas MucoviscidosisCiter ce document
H.H. Jarosz-Griffiths et al., « Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis. », Serveur académique Lausannois, ID : 10.7554/eLife.54556
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Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature with increased IL-18, IL-1β, 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-1β 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-1β 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-1β and pro-IL-1β 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.