Background. The possibility of monitoring the inflammatory response in a IL-8 transgenic WT and CF non invasive animal model has been demonstrated in this project. Experimental support has been provided for the proposal that azithromycin (AZM) acts by inhibiting the synthesis of bacterial metalloproteases (MPs) thus causing a mitigation of the lung inflammation. The possibility of further take advantage of the CF mouse model to analyze the possible anti-inflammatory activity of other antibiotics with mechanism of action similar to that of AZM and  that of inhibitors of human metallo-proteases appears of high interest.

Objectives and Methods. The objectives of this new part of the project are i) to use the IL-8 transgenic CF mouse model to monitoring the expected significant reduction of the pro-inflammatory response induced by Pseudomonas MPs by using protease inhibitors such as Galardin and other approved drugs for human use, namely Marimastat and the antibiotic Doxycycline and ii) to analyze the possible anti-inflammatory activity of other antibiotics with mechanism of action similar to that of AZM and used in CF such as claritromycin (CLAR) and tobramycin (TOB).