G Pang, M Ortega, R Zighang, G Reeves and R Clancy
Discipline of Pathology, Faculty of Medicine, University of Newcastle, New South Wales, Australia.

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.

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