Ceramide in cystic fibrosis

摘要

Cystic fibrosis (CF), the most common autosomal recessive disorder, at least in western countries, is caused by mutations of CFTR. The disease affects the intestine, the pancreas and the liver, but most important for life quality and expectance of CF patients are alterations in lung functions. The present review describes a novel pathway to explain many aspects of the pathogenesis of CF: ceramide accumulates in bronchial, tracheal and intestinal epithelial cells, and causes pulmonary inflammation, infection susceptibility, peribronchial collagen deposition and cell death, with the consequence of DNA release into the bronchial lumen and concomitant reduction of mucociliary clearance. All of these pathophysiological events are corrected by the normalization of pulmonary ceramide. Phase IIa and IIb clinical studies indicate a beneficial effect of a pharmacological inhibition of acid sphingomyelinase on lung functions in patients with CF.