Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects

• Published in: American journal of respiratory and critical care medicine Vol. 152; no. 1; p. 76
• Main Authors: Thomas, P S, Yates, D H, Barnes, P J
• Format: Journal Article
• Language: English
• Published: United States 01-07-1995
• Subjects: Adult; Aerosols; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - physiopathology; Bronchial Provocation Tests; Cell Count; Cross-Over Studies; Female; Humans; Male; Methacholine Chloride; Neutrophils - cytology; Recombinant Proteins - pharmacology; Spirometry; Sputum - cytology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1073-449X
• DOI: 10.1164/ajrccm.152.1.7599866

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.