Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo

Our data indicate that the CFTR-molecule functions as a transporter for sphingosine-1-phosphate and sphingosine or regulates the uptake of these sphingolipids by epithelial cells. The disturbed uptake of sphingosine and sphingosine-1-phosphate over the cell membrane results in an accumulation of ceramide in the cell membrane, which finally triggers a pro-inflammatory and pro-apoptotic status in the respiratory tract of cystic fibrosis patients. Amitriptyline reduces the cera-mide levels in the lung tissue, normalises the activity of cytokines and prevents constitutive cell death of epithelial cells observed in CFTR-deficient mice. Most important, amitriptyline prevents pulmonary infections of CFTR-deficient mice with P. aeruginosa. These effects of amitriptyline may result in an improved lung function of cystic fibrosis patients.