BACKGROUND: Resistin is an immunometabolic mediator that is elevated in several 
inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates 
the recruitment and activation of myeloid cells, notably neutrophils. 
Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due 
to the release of human neutrophil elastase- and myeloperoxidase-rich primary 
granules, leading to tissue damage. Here we assessed the relationship of 
resistin to CF lung disease.
METHODS: Resistin levels were measured in plasma and sputum from three 
retrospective CF cohorts spanning a wide range of disease. We also assessed the 
ability of neutrophils to secrete resistin upon activation in vitro. Finally, we 
constructed a multivariate model assessing the relationship between resistin 
levels and lung function.
RESULTS: Plasma resistin levels were only marginally higher in CF than in 
healthy control subjects. By contrast, sputum resistin levels were very high in 
CF, reaching 50-100 fold higher levels than in plasma. Among CF patients, higher 
plasma resistin levels were associated with allergic bronchopulmonary 
aspergillosis, and higher sputum resistin levels were associated with CF-related 
diabetes. Mechanistically, in vitro release of neutrophil primary granules was 
concomitant with resistin secretion. Overall, sputum resistin levels were 
negatively correlated with CF lung function, independently of other variables 
(age, sex, and genotype).
CONCLUSIONS: Our data establish relationships between resistin levels in the 
plasma and sputum of CF patients that correlate with disease status, and 
identify resistin as a novel mechanistic link between neutrophilic inflammation 
and lung disease in CF.