Chemoattractants and cytokines in primary ciliary dyskinesia and cystic fibrosis: Key players in chronic respiratory diseases

Abstract

Patients with primary ciliary dyskinesia (PCD) and cystic fibrosis (CF), two inherited disorders, suffer from recurrent airway infections characterized by persistent bacterial colonization and uncontrollable inflammation. Although present in high counts, neutrophils fail to clear infection in the airways. High levels of C-X-C motif chemokine ligand 8/interleukin-8 (CXCL8/IL-8), the most potent chemokine to attract neutrophils to sites of infection, are detected in the sputum of both patient groups and might cause the high neutrophil influx in the airways. Furthermore, in CF, airway neutrophils are highly activated because of the genetic defect and the high levels of proinflammatory chemoattractants and cytokines (e.g., CXCL8/IL-8, tumor necrosis factor-α and IL-17). The overactive state of neutrophils leads to lung damage and fuels the vicious circle of infection, excessive inflammation and tissue damage. The inflammatory process in CF airways is well characterized, whereas the lung pathology in PCD is far less studied. The knowledge of CF lung pathology could be useful to guide molecular investigations of the inflammatory processes in PCD lungs. Current available therapies can not completely remedy the chronic airway infections in these diseases. This review gives an overview of the role that chemoattractants and cytokines play in these neutrophil-dominated lung pathologies. Finally, the most frequently applied treatments in CF and PCD and new experimental therapies to reduce neutrophil-dominated airway inflammation are described.