Desensitisation of neutrophil responses by systemic interleukin 8 in cystic fibrosis.
BACKGROUND
Inflammation associated with neutrophil infiltration is a commonly observed feature of children with cystic fibrosis. Production of the major neutrophil chemotactic cytokine interleukin 8 (IL-8) is potentially of great importance in the pathology of cystic fibrosis. Concentrations of IL-8 in both sputum and bronchoalveolar lavage fluid have been found to be higher in children with cystic fibrosis than in controls. The IL-8 induced chemotactic response and numbers of IL-8 receptors on peripheral neutrophils obtained from children with cystic fibrosis have been compared with a control group of children.


METHODS
Cells were isolated from 18 patients with cystic fibrosis (aged 4-20 years) and 13 controls (aged 5-12 years) by dextran centrifugation followed by separation on Lymphoprep. Chemotaxis was assayed using multiwell microchemotaxis chambers and 5 microns polycarbonate filters. Filters were fixed and stained with Haema-Gurr for counting. Results were expressed as numbers of neutrophils per high power field (HPF).


RESULTS
At the optimum concentration (1 x 10(-8) mol/l) the number of cells migrating were similar for controls (150 (12)/HPF) and for the cystic fibrosis group (140 (14)/HPF)). At lower concentrations the numbers of neutrophils migrating were lower for the cystic fibrosis group. Scatchard analysis of 125I-labelled IL-8 binding revealed lower numbers of receptors on neutrophils from patients with cystic fibrosis (22,000 per cell) than from controls (75,000 per cell).


CONCLUSIONS
Reduced responsiveness to IL-8 of neutrophils from patients with cystic fibrosis is associated with receptor desensitisation as a result of exposure to high systemic levels of IL-8.
Dai
Y
Y
University of Southampton, UK.
Dean
T P
TP
Church
M K
MK
Warner
J O
JO
Shute
J K
JK
D000293:Adolescent; D000328:Adult; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology*; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D018123:Receptors, Interleukin / Q000032:analysis; D023062:Receptors, Interleukin-8A
D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A