NITRIC-OXIDE AND INTERLEUKIN-8 AS INFLAMMATORY COMPONENTS OF CYSTIC-FIBROSIS

We examined the production of reactive nitrogen intermediates in the t racheo-bronchial tree of patients with cystic fibrosis (CF). Examinati on of the soluble phase of sputa from 17 CF patients revealed the pres ence of high levels of NO2-/NO3- assayed by the Greiss reaction. We al so examined the presence of the chemotactic cytokine interleukin-8 (IL -8) in these samples so as to assess another important inflammatory ma rker; high levels of IL-8 were present in the sputa of cystic fibrosis subjects. The elevated nitrite was not produced by the presence of Ps eudomonos bacteria in the sputa, inasmuch as bacteria in culture relea sed undetectable amounts of nitrite in culture media. Neutrophils from the sputa of CF patients with disease exacerbation released higher am ounts of nitrite and IL-8. Neutrophils from the sputa were also shown to spontaneously release substantial amounts of nitrite in the superna tants, and this release was partly blocked by the antagonist N-G-monom ethyl-L-arginine (L-NMMA). Blood neutrophils were shown to release nit rite only in response to challenge with CF-associated strains of Pseud omonas, and not exposure to cytokines. There was no significant differ ences in nitrite release between normal and CF blood polymorphonuclear leucocytes (PMNs). A study of upper airway epithelial cell lines show ed that these cells released low amounts of nitrite after infection wi th CF-associated strains of Pseudomonas but not after cytokine exposur e. Epithelial cell lines with CF or normal phenotypes were shown to re lease similar quantities of nitrite, upon stimulation with Pseudomonas . These data demonstrate that elevated levels of reactive nitrogen int ermediates and IL-8 are produced in the tracheo-bronchial tree of subj ects with CF. Levels of IL-8 and nitrite were higher in the secretions of CF subjects with disease exacerbation. The involvement of nitric o xide and other reactive nitrogen intermediates produced by neutrophils and other cells in the tissue damaging processes in CF deserves furth er investigation.