Cytokine-ion channel interactions in pulmonary inflammation

The lower airways represent an integral part of the respiratory system, passing oxygen from the alveolar space into the capillary bed and removing CO2 from the blood. To that purpose, it is crucial that the majority of the 266 million alveoli in an adult human lung remain dry and that the alveolar-capillary barriers are tight. Vectorial sodium transport through the apically expressed epithelial sodium channel (ENaC) and the basolateral sodium-potassium pump (Na+-K+-ATPase) in alveolar epithelial cells is crucial for alveolar liquid clearance. These pathways are moreover either negatively or positively affected by the direction of chloride transport through the cystic fibrosis transmembrane conductance regulator (CFTR). Failure to control lung liquid clearance can lead to the development of pulmonary permeability edema. Inflammatory cytokines and chemokines, induced during bacterial and viral infection, such as TNF, IFN-γ, TGF-β1, IL-1β, IL-8 and KGF were shown to affect alveolar liquid clearance, since they can alter ion channel and barrier function, through a complex multitude of mechanisms.
This research topic will review recent developments in this field, with relevance to disease states, such as pneumonia, ARDS and ischemia-reperfusion-induced lung injury. A better knowledge of the complex interactions between inflammatory cytokines and ion channels can foster the development of novel therapies towards pulmonary edema.