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 inflammatory response in lungs of patients with CF might be directly related to defects in epithelial cell cystic fibrosis transmembrane regulator.

Objective: We sought to determine the relationship of epithelial cell cytokine production to CF lung disease.

Methods: Immunofluorescence and cultures of freshly obtained bronchial epithelial cells and ELISA for IL-10, IL-8, and IL-6 were used to study alterations in epithelial cell cytokine production.

Results: Fresh bronchial epithelial cells from healthy control subjects (HCs) secreted 98 +/- 20 pg/mL of the anti-inflammatory cytokine IL-10 when placed 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 IL-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 between the immunofluorescent staining of fresh bronchial epithelial cells from both the HCs and patients with CF and the concentrations of cytokines in epithelial lining fluid suggests a reciprocal relationship between anti-inflammatory (IL-10) and proinflammatory (IL-6 and IL-8) cytokine production by the epithelial cells in HCs versus patients with CF.

Conclusions: Alterations in epithelial cell cytokine production in the lungs of patients with CF may contribute to the excessive local inflammation.