L-Arginine Deficiency in Cystic Fibrosis Lung Disease

Cystic fibrosis affects multiple organs but lung disease remains the major determinant of patient morbidity and mortality. Cystic fibrosis lung disease is characterized by chronic infection and inflammation. The amino acid L-arginine is substrate for both nitric oxide synthases and arginases. The activity of arginase in sputum is increased while the production of nitric oxide is reduced in the cystic fibrosis airways. Nitric oxide deficiency in cystic fibrosis contributes to the susceptibility to certain bacterial infections of the airways. Arginase activity in the cystic fibrosis airways correlates with nitric oxide production and pulmonary function. Treatment leading to a decrease in arginase activity also results in increased airway nitric oxide production and improved pulmonary function in cystic fibrosis. Similarly, L-arginine supplementation is followed by increased airway nitric oxide production, and nebulized inhaled L-arginine not only improved exhaled nitric oxide concentrations but also increased pulmonary function in patients with cystic fibrosis. These finding suggest that treatment targeting the imbalance of nitric oxide synthase and arginase in the cystic fibrosis airways may improve host defense as well as airway obstruction in these patients.