IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.

Abstract

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.

DOI: 10.1038/ncomms10791

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@article{Iannitti2016IL1RA, title={IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.}, author={Rossana Giulietta Iannitti and Valerio Napolioni and Vasilis Oikonomou and Antonella de Luca and Claudia Galosi and Marilena Pariano and Cristina Massi-Benedetti and M{\^o}nica M Borghi and Matteo Puccetti and Vincenzina Lucidi and Carla Colombo and Ersilia Vita Fiscarelli and Cornelia Lass-Fl{\"{o}rl and Fabio Majo and Lisa Cariani and Maria Chiara Russo and Luigi Porcaro and Gabriella Ricciotti and Helmut Ellemunter and Luigi Ratclif and Fernando Maria de Benedictis and Vincenzo Nicola Talesa and Charles Anthony Dinarello and Frank Leo van de Veerdonk and Luigina Romani}, journal={Nature communications}, year={2016}, volume={7}, pages={10791} }