Targeting Lung Inflammation in Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease found mostly in the Caucasian population; a major complication of CF that often leads to mortality is lung inflammation. Playing a key role in the inflammation, as demonstrated by several studies, is the continuous recruitment of neutrophils to the lung [1-3]. Despite these millions of activated neutrophils, CF patients cannot adequately defend against invading pathogens because the bactericidal activity of the neutrophils in CF patients is dysregulated [4,5] due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene [6]. When pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and several species of Mycobaterium and Burkholera colonize in the lung airways, neutrophils are continuously drawn to the site and cause a persistent inflammatory response [7]. The severity of airway inflammation varies widely even among patients who are homozygous for the most common mutation in CFTR, DF508 [8]. The underlying mechanisms that cause neutrophils to lose their function for pathogen clearance are not well understood; therefore, effective pharmacological approaches are lacking.