Researchers aimed at setting-up a convenient, non-invasive, in vivo imaging model to monitor lung inflammation in CF mice with Pseudomonas aeruginosa (Pa) acute lung infection, and to evaluate the possible anti-inflammatory effects of molecules interfering with proteases, such as protease inhibitors Marimastat and Ilomastat. Pa acute lung infection was established by intratracheal instillation in wild-type (WT ) and CFTR-knockout (KO) C57BL/6 transgenic mice expressing the luciferase gene under control of bovine IL-8 promoter. The infection induced IL-8-dependent bioluminescence emission indicating lung inflammation. In infected mice with ongoing inflammation, intratracheal treatment with 150μM Marimastat and Ilomastat reduced the bioluminescence signal in comparison to untreated, infected animals. No adverse effects due to treatment with protease inhibitors were observed in mice. These results show that protease inhibition elicits beneficial effects in mice by reducing the lung inflammation caused by Pa infection. Thus, Ilomastat and Marimastat might be potential candidate molecules for the treatment of patients with Pa infection, encouraging further studies on protease inhibitors and their possible application in cystic fibrosis. Particularly, inhalable formulations could be a preferential therapy for CF patients, allowing local airways treatment.

Congress abstracts

– Sandri A, Lleo MM, Boschi F “Protease inhibitors elicit anti-inflammatory effects in mice with Pseudomonas aeruginosa acute lung infection”, 42nd European Cystic Fibrosis Conference, 5-8 June 2019, Liverpool, UK