title: Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis.
abstract: Inflammation plays a critical role in lung disease progression in cystic fibrosis (CF). This inflammatory process is dominated by a neutrophil influx in the airways. To determine whether the accumulation of neutrophils in the airways of CF patients is associated with an altered function, we analyzed the capacity of neutrophils isolated from the lung compartment and the blood to release the major neutrophil pro- and anti-inflammatory cytokines IL-8 and IL-1-receptor antagonist (ra) spontaneously and in the presence of LPS. Comparison of cytokine production by blood neutrophils from CF patients and from control subjects showed significantly increased IL-8 and decreased IL-1ra release by CF neutrophils. Comparison of cytokine production by airway and blood neutrophils from CF patients also documented distinct profiles: the spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils. Culture in the presence of LPS failed to further enhance cytokine production. Analysis of the effect of dexamethasone confirmed the difference in the responsiveness of lung and blood neutrophils in CF. Used at a concentration effective in reducing IL-8 production by blood neutrophils, dexamethasone (10(-6) M) was unable to repress secretion of IL-8 by airway neutrophils. In addition, comparison of cytokine production by airway neutrophils from children with CF and children with dyskinetic cilia syndrome also documented distinct profiles of secretion. These results are consistent with a dysregulated cytokine production by lung and blood neutrophils in CF. They provide support to the hypothesis that not only the CF genotype but also the local environment may modify the functional properties of the neutrophils.
authors.affiliation: Departement de Pneumologie Pediatrique-Institut National de la Santé et de la Recherche Médicale E213, Hopital Armand Trousseau, 75012 Paris, France.
authors.forename: Harriet
authors.initials: H
authors.lastname: Corvol
authors.forename: Catherine
authors.initials: C
authors.lastname: Fitting
authors.forename: Katarina
authors.initials: K
authors.lastname: Chadelat
authors.forename: Jacky
authors.initials: J
authors.lastname: Jacquot
authors.forename: Olivier
authors.initials: O
authors.lastname: Tabary
authors.forename: Michele
authors.initials: M
authors.lastname: Boule
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: Annick
authors.initials: A
authors.lastname: Clement
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000276:immunology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D012795:Sialoglycoproteins; D003907:Dexamethasone