The protease-antiprotease battle in the cystic fibrosis lung

It is well recognized that long-standing inflammation damages the lungs in children and adults with cystic fibrosis (CF), and it is no coincidence that most CF deaths are due to respiratory failure. The lung inflammation is primarily due to the host response to chronic bacterial infection, particularly with Pseudomonas aeruginosa, which calls into question the whole concept of colonization, with its implication of bacteria residing harmlessly in the body. However, it has also been suggested that inflammation may actually precede microbial infection in the CF lung, an idea based on the fact that significant inflammation has been detected in broncho-alveolar lavage (BAL) samples in which microbes (bacteria, viruses or fungi) were not isolatedl2. It is possible that in the young patients studied the infection had been eradicated but that the resultant inflammation simply persisted3. In older children, however, it is unlikely that the pathogenic bacteria are ever eradicated. In addition, using more sensitive molecular techniques for identifying bacteria, it may be that infection is going unrecognized when standard culture methods are employed4. More recently, it has been suggested that inflammation may be an integral part of the CF defect. Accumulation of faulty CFTR (CF transmembrane conductance regulator) protein in the cell endoplasmic reticulum may result in production of proinflammatory cytokines following activation of the transcription factor NFKB5. In conclusion, it seems most likely that the majority of lung inflammation is in fact secondary to recurrent bacterial or viral infections, but that there is a contribution from endogenous factors, and possibly even a reaction to the abnormal mucus lining the epithelium. It is still unexplained why the production of interleukin-10, an important anti-inflammatory cytokine, is reduced in CF epithelial cells67.