Altered respiratory epithelial cell cytokine production in cystic fibrosis

Background: Reports that lung inflammation in patients with cystic fibrosis (CF) might precede infection raise the possibility that the excessive infl ammatory response in lungs of patients with CF might be directly related to defects in epithelial cell cystic fibrosis transmembrane regulator, Object ive: We sought to determine the relationship of epithelial cell cytokine pr oduction to CF lung disease, Methods: Immunofluorescence and cultures of freshly obtained bronchial epit helial cells and ELISA for IL-10, IL-8. and IL-6 were used to study alterat ions in epithelial cell cytokine production, Results: Fresh bronchial epithelial cells from healthy control subjects (HC s) secreted 98 +/- 20 pg/mL of the anti-inflammatory cytokine IL-10 when pl aced in primary culture in vitro but little or no IL-8 or IL-6, In contrast , fresh epithelial cells from patients with CF did not secrete detectable I L-10 but produced 38 +/- 17 pg/mL IL-8 and 40 +/- 17 pg/mL IL-6. These data correlated very well with the immunofluorescence data. The correlation bet ween the immunofluorescent staining of fresh bronchial epithelial cells fro m both the HCs and patients with CF and the concentrations of cytokines in epithelial lining fluid suggests a reciprocal relationship between anti-inf lammatory (IL-10) and proinflammatory (IL-6 and IL-8) cytokine production b y the epithelial cells in HCs versus patients with CF, Conclusions: Alterations in epithelial cell cytokine production in the lung s of patients with CF may contribute to the excessive local inflammation.