Inflammation and CFTR: might neutrophils be the key in cystic fibrosis?

THE aim of this hypothesis is to provide new insights into the still unclea r mechanisms governing airway inflammation in cystic fibrosis. Although the genetic basis of cystic fibrosis as well as the molecular structure of cys tic fibrosis transmembrane regulator (CFTR), the mutated protein which caus es the disease, have been well defined, a clear relationship between the ge netic defect and the pulmonary pathophysiology, especially chronic infectio ns and neutrophil-dominated airway inflammation has not been established. C ystic fibrosis is thus a unique pathological situation Ln that neutrophils can be depicted as both an antiinfectious and a proinflammatory cell. In cy stic fibrosis there is an emerging picture of an imbalance between these tw o roles with both a reduction in the antiinfectious efficacy and an aug men tation of the proinflammatory functions. Better knowledge of fundamental de fects in neutrophil function in cystic fibrosis as well as a novel cellular function of CFTR, which will be reviewed, will allow identification of pot entially new clinical targets and aid selective therapeutic action aimed at counteracting the lethal neutrophil-induced airway inflammation. The ratio nale for colchicine therapy is a significant example of a drug which might act both at the molecular levels on CFTR expression in epithelial cells and on neutrophils to mediate antiinflammatory effects. Preliminary results ar e presented in this issue (Med Inflamm 1999; 8: 13-15).