Inflammation remains predominant in progressive cystic fibrosis (CF) lung damage in cystic and new anti-inflammatory drugs replacing corticosteroids or ibuprofen are to be searched. Thanks to previous FFC grants these researchers described the characteristics of two molecules already tested for efficacy and safety in clinical pharmacology: beta-sitosterol (BSS) and miglustat. They have shown that BSS exerts anti-inflammatory activity in CF bronchial cells and the enantiomer L-miglustat produces an anti-inflammatory effect in mice infected by Pseudomonas aeruginosa. The aim of this project is to push forward the translational application of these molecules: therefore BSS, commercially available, and the enantiomer L-miglustat, de novo synthesized and purified, will be tested in murine models of lung infection. Their effect on inflammatory response will be tested in terms of: i) safety; ii) evaluation of lung inflammation; iii) ability of mice to clear bacteria. The most effective molecule will be validated in CF mice. The final object is to repurpose BSS and L-miglustat in cystic fibrosis ad to provide proof of concept data for planning clinical trials.