Autocrine modulation of IL-8 production by sputum neutrophils in chronic bronchial sepsis.
We examined the activity of neutrophils isolated from sputum and blood of subjects with chronic bronchial sepsis in terms of interleukin-8 (IL-8), IL-1beta, and tumor necrosis factor-alpha (TNF alpha) production. In sputum, the numbers of neutrophils correlated with the concentrations of these cytokines. Sputum neutrophils constitutively secreted large amounts of IL-8, IL-1beta, and TNF alpha. The patterns of secretion, however, differed from those of blood neutrophils stimulated with bacterial lipopolysaccharide (LPS). Cytokine secretion was time-dependent and was inhibited by cycloheximide and dexamethasone. IL-10 inhibition of IL-8 production by sputum neutrophils was significantly less than that noted with activated neutrophils. Antibody to IL-1beta but not to TNF alpha, inhibited IL-8 secretion by sputum neutrophils, contrasting with results found using blood neutrophils. Incubation of blood neutrophils in sputum sol induced a similar cytokine secretion profile to that following exposure to LPS. The inhibitory effects on IL-8 protein production correlated with messenger RNA (mRNA) gene expression. These observations indicate that neutrophils are a significant source of IL-8 in purulent sputum, and that an autocrine loop involving IL-1beta maintains secretion within the bronchus lumen.
Pang
G
G
Discipline of Pathology, Faculty of Medicine, University of Newcastle, New South Wales, Australia.
Ortega
M
M
Zighang
R
R
Reeves
G
G
Clancy
R
R
D001769:Blood / Q000187:drug effects / Q000378:metabolism; D001987:Bronchiectasis / Q000378:metabolism*; D002908:Chronic Disease; D003513:Cycloheximide / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000302:isolation & purification; D013183:Sputum / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D016209:Interleukin-8; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide