INTERLEUKIN-8 PRODUCTION BY CYSTIC-FIBROSIS NASAL EPITHELIAL-CELLS AFTER TUMOR-NECROSIS-FACTOR-ALPHA AND RESPIRATORY SYNCYTIAL VIRUS STIMULATION

High levels of neutrophils and the neutropil-attracting chemokine inte rleukin (IL)-8 have been observed in the airways of patients with cyst ic fibrosis (CF). We hypothesized that CF respiratory epithelium produ ces excessive amounts of IL-8 either at baseline or after stimulation. To test this hypothesis we compared immunoreactive IL-8 release by pr imary nasal epithelial cell (NEC) cultures established from young chil dren with or without CF, at several time points after stimulation of c ultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV). Both stimuli induced significantly increased IL-8 release by both CF and control cultures. However, ther e was no difference between CF and control cells in either the magnitu de or duration of the IL-8 response. The effect of transduction of CF cells with Ad5-CBCFTR, an adenovirus vector mediating expression of cy stic fibrosis transmembrane regulator (CFTR), on IL-8 production was a lso determined. TNF-alpha stimulated IL-8 production was not different in Ad5-CBCFTR-transduced, -untransduced, or Ad5-CMVLacZ-transduced co ntrol cells. Lastly, immortalized CF tracheal epithelial cell lines, b oth uncorrected and retrovirally corrected with CFTR, were compared. A gain, TNF-alpha-stimulated IL-8 production did not differ significantl y between cell lines with and without functioning CFTR. Our data sugge st that isolated CF NECs cultured under these conditions do not produc e more IL-8 than do non-CF control cultures, either at baseline or aft er incubation with the nonspecific stimuli TNF-alpha and RSV. We concl ude that the absence of functioning CFTR alone is not sufficient to ca use excessive production of IL-8.