Reduced interleukin-8 production by cystic fibrosis airway epithelial cells

The acquisition of Pseudomonas aeruginosa in the airways of patients with c ystic fibrosis (CF) is the initial event leading to bronchiectasis and lung disease. Although the host factors that permit initial airway colonization are largely unknown, recent studies suggest that secretion of interleukin (IL)-8 by airway epithelia and local recruitment of neutrophils is the fina l pathway in a pulmonary cytokine network. To determine whether differences in cytokine production exist between normal and CF airway epithelia, secre tion of immunoreactive IL-8 and IL-10 as well as specific messenger RNA (mR NA) abundance were compared in airway epithelia expressing normal and mutan t CF transmembrane regulator. After induction with IL-1 beta, a CF airway c ell line engineered to express the wild-type CF gene (CFT1-LCFSN) secreted significantly more immunoreactive IL-8 than did its isogenic parent that ex pressed the mutant CF gene (CFT1) or an isogenic vector control line (CFT1- LC3). Further studies with the three related cell lines demonstrated that e xpression of CFT1-LCFSN was associated with a significant increase in unind uced secretion of immunoreactive IL-8 as well as a 10- to 20-fold increase in IL-8 mRNA abundance when compared with the isogenic lines expressing the mutant gene. IL-1 beta induction and intracellular accumulation of IL-8 ap peared to be unaffected by CF genotype. These studies suggest that IL-8 sec retion by CF airway epithelial cells is defective and may contribute to Pse udomonas persistence in the CF airway. Further studies are needed to confir m this difference in other cell lines and determine the linkage between IL- 8 production and CF gene expression.