Increased levels of nitric oxide and leukotriene B-4 in serum of patients with cystic fibrosis

Chronic progressive lung disease is the leading cause of death in patients with cystic fibrosis (CF). The lung pathology is characterized by severe neutrophil-dominated inflammation with progressive fibrosis and loss of pulmonary function. Leukotriene B-4 (LTB(4)) plays a key role in the pathophysiology of CF by recruiting activated neutrophils at sites of injury. Nitric oxide (NO), a highly reactive free radical molecule, may also function as a mediator of inflammation in lung diseases. The purpose of this study was to ascertain whether NO is produced in patients with CF and to determine a possible relationship between NO and LTB(4) levels in CF. Seven patients with CF and 10 healthy volunteers were used in the present study. Assessment of CF was based on positive sputum cultures for Pseudomonas aeruginosa. Levels of NO and LTB(4) were measured in the sera of patients with CF and normal controls using the Griess reaction for NO and radioimmunoassay for LTB(4) detection. Both levels of NO and LTB(4) in the sera of the CF patients were significantly elevated compared to the control group. A significant direct correlation between levels of NO and LTB(4) in patients with CF also existed. Data from this study suggest that LTB(4)-induced lung injury in CF may be mediated by NO released from alveolar macrophages and/or neutrophils. Therefore, therapy aimed at blocking the production of NO and LTB(4) may prove beneficial in treating patients with CF.