Abstract
Despite the high expectations associated with the recent introduction of CFTR modulators, airway inflammation still remains a relevant clinical issue in cystic fibrosis (CF). The classical anti-inflammatory drugs have shown very limited efficacy, when not being harmful, raising the question of whether alternative approaches should be undertaken. Thus, a better knowledge of the mechanisms underlying the aberrant inflammation observed in CF is pivotal to develop more efficacious pharmacology. In this respect, the observation that endogenous proresolving pathways are defective in CF and that proresolving mediators, physiologically generated during an acute inflammatory reaction, do not completely suppress inflammation, but promote resolution, tissue healing and microbial clearance, without compromising immune host defense mechanisms, opens interesting therapeutic scenarios for CF. In this mini-review, we present the current knowledge and perspectives of proresolving pharmacology in CF, focusing on the specialized proresolving lipid mediators and selected peptides.
Highlights
Pulmonary inflammation and infection, leading to lung failure, represent the main cause of morbidity and mortality in individuals with cystic fibrosis (CF) (Cantin et al, 2015)
A partial answer to this question may be Inflammation Resolution in Cystic Fibrosis provided by a subsequent study of the GOAL trial, showing a downward trend in the relative abundance of P. aeruginosa and S. aureus in the airways of study participants treated with ivacaftor, but no changes in interleukin (IL)-6, -8, -1b, and free elastase in sputum (Rowe et al, 2014; Heltshe et al, 2015)
specialized proresolving lipid mediators (SPM) act at multiple levels on cells and mechanisms involved in the pathophysiology of CF airway inflammation and activated resolution of inflammation and infection in preclinical and clinical studies, providing evidence for resolution pharmacology based on SPM in CF
Summary
A better knowledge of the mechanisms underlying the aberrant inflammation observed in CF is pivotal to develop more efficacious pharmacology In this respect, the observation that endogenous proresolving pathways are defective in CF and that proresolving mediators, physiologically generated during an acute inflammatory reaction, do not completely suppress inflammation, but promote resolution, tissue healing and microbial clearance, without compromising immune host defense mechanisms, opens interesting therapeutic scenarios for CF. The observation that endogenous proresolving pathways are defective in CF and that proresolving mediators, physiologically generated during an acute inflammatory reaction, do not completely suppress inflammation, but promote resolution, tissue healing and microbial clearance, without compromising immune host defense mechanisms, opens interesting therapeutic scenarios for CF In this mini-review, we present the current knowledge and perspectives of proresolving pharmacology in CF, focusing on the specialized proresolving lipid mediators and selected peptides
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