title: Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects.
abstract: The effect of inhaled recombinant human tumor necrosis factor-alpha (rhTNF alpha) on airway responsiveness and the cellular composition of sputum was studied in eight normal subjects using a placebo-controlled study design. Spirometric data and bronchial responsiveness (BR) to methacholine were studied, and an estimate of pulmonary-cell infiltration was made using the technique of induced sputum. A single dose of rhTNF alpha (60 ng) caused an increase in BR, with a leftward shift in the concentration-based response to methacholine at all time points after inhalation, as compared with a saline control challenge. Likewise, there was a decrease in the log provocative concentration of methacholine causing a 15% decrease in FEV1, which reached a maximum at 24 h (1.37 +/- 0.22 versus 1.87 +/- 0.24, rhTNF alpha and control, respectively; p < 0.05). No change was observed in baseline spirometric measures at any of the time points. A significant increase in the percentage of neutrophils occurred in the induced sputum, reaching a maximum at 24 h (44.2 +/- 9.9% versus 16.6 +/- 7.1%, rhTNF alpha and control, respectively; p < 0.05). We conclude that TNF alpha can induce an increase in airway responsiveness in normal subjects, and is associated with a neutrophil infiltration, thus making it a candidate cytokine for the induction of airway inflammation and hyperresponsiveness.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
authors.forename: P S
authors.initials: PS
authors.lastname: Thomas
authors.forename: D H
authors.initials: DH
authors.lastname: Yates
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000328:Adult; D000336:Aerosols; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002452:Cell Count; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D009504:Neutrophils / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013147:Spirometry; D013183:Sputum / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000336:Aerosols; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride