Reduced neutrophil elastase inhibitor elafin and elevated TGFβ1 are linked to inflammatory response in sputum of CF patients with Pseudomonas aeruginosa

Research questionPulmonary disease progression in patients with cystic fibrosis (CF) is characterized by inflammation and fibrosis, and aggravated by Pseudomonas aeruginosa (Pa). We investigated the impact of Pa specifically 1) on protease/antiprotease balance and 2) inflammation, as well as 3) the link of both parameters to clinical parameters of CF-patients.MethodsTGFβ1, IL1β, IL8, neutrophil elastase (NE) and elastase inhibitor elafin were measured (ELISA assays), and gene expression of the NF-ĸB pathway was assessed (RT-PCR) in the sputum of 60 CF-patients with a minimum age of 5 years. Spirometry was assessed according to ATS guidelines.Results1) NE was markedly increased in Pa-positive sputum, whereas elafin was significantly decreased. 2) Increased IL1β/IL8 were associated with both Pa infection and reduced FEV1, as well as sputum TGFβ1 was elevated in Pa-infected CF-patients and linked to an impaired lung function. 3) Moreover, gene expression of NF-ĸB signaling components was increased in sputum of Pa-infected patients; these findings were positively correlated with IL8.ConclusionOur study links Pa infection to an imbalance of NE and NE-inhibitor elafin and increased inflammatory mediators. Moreover, our data demonstrate an association between high TGFβ1 sputum levels and a progress in chronic lung inflammation and pulmonary fibrosis in CF. Controlling the excessive airway inflammation by inhibition of NE and TGFβ1 might be promising therapeutic strategies in future CF therapy and a possible complement to CFTR-modulators.