Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis.
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.
Corvol
Harriet
H
Departement de Pneumologie Pediatrique-Institut National de la Santé et de la Recherche Médicale E213, Hopital Armand Trousseau, 75012 Paris, France.
Fitting
Catherine
C
Chadelat
Katarina
K
Jacquot
Jacky
J
Tabary
Olivier
O
Boule
Michele
M
Cavaillon
Jean-Marc
JM
Clement
Annick
A
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
D005938:Glucocorticoids; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D012795:Sialoglycoproteins; D003907:Dexamethasone