ALTERED CYTOKINE PRODUCTION BY CYSTIC-FIBROSIS TRACHEAL GLAND SEROUS CELLS

Human submucosal tracheal glands are now believed to play a major role in the physiopathology of cystic fibrosis (CF). We successfully devel oped techniques for culturing human tracheal gland serous cells from n ormal individuals (HTGS cells) and from CF patients (CF-HTGS cells) an d have shown that the cultured cells have retained most of their in vi vo epithelial and secretory characteristics. In order to determine to what extent the serous cells may participate in the lung defense again st infection, we examined the effects of the lipopolysaccharide (LPS) of Pseudomonas aeruginosa on HTGS and CF-HTGS cells, with special refe rence to tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) , and IL-8 secretion. HTGS cells showed a daily basal secretion of IL- 6 (1.68 +/- 0.14 ng/10(6) cells) and IL-8 (9.6 +/- 1.3 ng/10(6) cells) and no constitutive secretion of TNF-alpha. Treatment with P. aerugin osa LPS resulted in a significant increase in the basal production of IL-6 (increase of 200% +/- 12%) and IL-8 (525% +/- 40%) as well as a r apid production of TNF-alpha (250 +/- 38 pg/10(6) cells). The LPS-indu ced secretion of IL-6 and IL-8, but not that of TNF-alpha, was inhibit ed by glucocorticoids, CF-HTGS cells showed a much higher basal secret ion of IL-6 (13.2 +/- 0.5 ng/10(6) cells) and IL-8 (45.6 +/- 7.2 ng/10 (6) cells) than normal cells. Treatment with the LPS of P. aeruginosa induced increased production of IL-6 (increase of 100% +/- 8%) and IL- 8 (55% +/- 18%) but did not induce the secretion of TNF-alpha. Neither intracellular TNF-alpha nor TNF-alpha transcripts were found in CF-HT GS cells, whereas they were found in normal HTGS cells. In addition, d examethasone was found to stimulate IL-6 and IL-8 secretion (in the pr esence or absence of LPS) but did not induce any secretion of TNF-alph a. All these data indicate that HTGS cells are responsive to P. aerugi nosa LPS, which results in an increased secretion of IL-6, IL-8, and T NF-alpha, the secretion of which appeared to he impaired in CF-HTGS ce lls.