Oxidative stress in cystic fibrosis lung disease: an early event, but worth targeting?

Oxidative stress is a universal biological response, which plays a major role in a variety of inflammatory disease conditions, such as cardiovascular diseases or sepsis. In the lung, harmful oxidative stress mainly occurs in nonresolving pathologies, such as cystic fibrosis (CF) lung disease [1, 2] or, to a lesser extent, chronic obstructive pulmonary disease [3, 4]. In CF, neutrophils are continuously recruited to the airways and liberate their toxic ingredients, particularly proteases and oxidants, in an uncontrolled fashion [5]. Anti-proteases and anti-oxidants shield the lung from free proteolytic and oxidative damage [6]. However, in CF the amount and duration of neutrophilic inflammation overwhelms these defence systems [2, 7]. The released proteases and reactive oxygen species, physiologically the neutrophil’s major armamentarium to kill intracellular pathogens, as evidenced in patients with chronic granulomatous disease [8], degrade extracellular matrix components and immune receptors and oxidise proteins in the CF airway microenvironment in an uncontrolled manner.