Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma

• Published in: Thorax Vol. 57; no. 9; pp. 774 - 778
• Main Authors: Thomas, P S, Heywood, G
• Format: Journal Article
• Language: English
• Published: London BMJ 01-09-2002; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Airway management; Allergens; Allergies; Asthma; Asthma - metabolism; Asthma - physiopathology; Biological and medical sciences; Bronchodilator Agents; Carbon Monoxide - metabolism; Cell Count; Chronic obstructive pulmonary disease, asthma; Cross-Over Studies; Cytokines; Double-Blind Method; Female; Forced Expiratory Volume - physiology; Humans; Male; Medical sciences; Methacholine Chloride; Nitric Oxide - metabolism; Original; Physiological aspects; Pneumology; RNA, Messenger - metabolism; Sputum - cytology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Australia; Human; Pharmacologic test; Pathophysiology; Respiratory disease; Cytokine; Exploration; Inflammation; Asthma; Inhalation; Respiratory tract; Lung function; Obstructive pulmonary disease; Tumor necrosis factor α
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thorax.57.9.774

Background: Inhaled tumour necrosis factor alpha (TNFα ) has previously been shown to induce airway neutrophilia and increased airway reactivity in normal subjects. It was hypothesised that a similar challenge would increase airway reactivity in those with mild asthma, but that the inflammatory profile may differ. Methods: Ten mild asthmatic subjects were recruited on the basis of clinical asthma and either a sensitivity to methacholine within the range defined for asthma or a 20% improvement in forced expiratory volume (FEV1) after 200 μg salbutamol. Subjects inhaled either vehicle control or 60 ng recombinant human (rh)TNFα and were studied at baseline, 6, 24, and 48 hours later. Variables included spirometric parameters, methacholine provocative concentration causing a 20% fall in FEV1 (PC20), induced sputum differential cell count, relative sputum level of mRNA of interleukins (IL)-4, IL-5, IL-9, IL-14, IL-15 and TNFα, and the exhaled gaseous markers of inflammation, nitric oxide and carbon monoxide. Results: PC20 showed an increase in sensitivity after TNFα compared with control (p<0.01). The mean percentage of neutrophils increased at 24–48 hours (24 hour control: 1.1 (95% CI 0.4 to 2.7) v 9.2 (95% CI 3.5 to 14.9), p<0.05), and there was also a rise in eosinophils (p=0.05). Relative levels of sputum mRNA suggested a rise in expression of TNFα , IL-14, and IL-15, but no change in IL-4 and IL-5. Spirometric parameters and exhaled gases showed no significant change. Conclusion: The increase in airway responsiveness and sputum inflammatory cell influx in response to rhTNFα indicates that TNFα may contribute to the airway inflammation that characterises asthma.