Proinflammatory cytokine responses to P-aeruginosa infection in human airway epithelial cell lines

A tendency toward excessive inflammation in cystic fibrosis (CF) patients o ften accompanies lung infections with Pseudomonas aeruginosa. We tested the cytokine response to P. aeruginosa in two pairs of human airway epithelial cell lines matched except for CF transmembrane conductance regulator activ ity. The 9/HTEo(-) CF-phenotypic cell line produced significantly more inte rleukin (IL)-8, IL-6, and granulocyte-macrophage colony-stimulating factor but not regulated on activation normal T cell expressed and secreted (RANTE S) in response to Pseudomonas than the 9/HTEo(-) control line, and the diff erences widened over time. Similarly, a 16HBE cell line lacking transmembra ne conductance regulator activity showed enhanced IL-8 and IL-6 responses c ompared with the control cell line. The pharmacology of the cytokine respon se also differed because dexamethasone reduced cytokine production to simil ar levels in the matched cell lines. The protracted proinflammatory cytokin e response of the CF-phenotypic cell lines suggests that the limiting mecha nisms of normal cells are absent or attenuated. These results are consisten t with in vivo observations in patients with CF and suggest that our novel cell lines may be useful for further investigation of the proinflammatory r esponses in CF airways.