Quantitative cytokine gene expression in CF airway.

Abstract

Bronchoalveolar lavage fluid (BALF) in cystic fibrosis (CF) shows increased inflammation, which could be due to abnormal cytokine regulation. Bronchial epithelial cells and migratory inflammatory cells produce these cytokines, but few quantitative in vivo data are available comparing young CF patients with controls. We hypothesized that IL-8 mRNA abundance was higher in young CF vs. non-CF disease control patients in lung epithelium and inflammatory cells. Bronchial epithelial cells (BEC) were obtained by brush biopsy, and airway inflammatory cells (BALFC) by bronchoalveolar lavage, in 17 CF and 21 non-CF patients <5 years old undergoing clinically indicated bronchoscopy. Cellular mRNA expression was quantified by real-time PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Abundance of IL-8/GAPDH in BEC was significantly higher in CF (14.8 +/- 3.3) than non-CF (4.2 +/- 0.6) samples, and this difference was also significant when patients were stratified according to infection. In BALFC, the difference in IL-8 expression did not reach statistical significance: CF (17.1 +/- 6.5) vs. non-CF (6.8 +/- 1.9), but BALF cell number/ml was significantly higher in CF. IL-10 mRNA was very low in all samples, without showing a decrease in CF vs. non-CF patients. We conclude that early in the disease, IL-8 mRNA expression in BEC is increased in CF in vivo. Although IL-8 mRNA in migratory cells was not significantly higher in CF, these cells may still contribute to elevated IL-8 in airway secretions, secondary to increased cell density in BALF.