ORIGINAL ARTICLE

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

P S Thomas, G Heywood

Inflammation Research Unit, School of Pathology, Faculty of Medicine, University of New South Wales, Sydney, Australia and Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW 2031

Correspondence to:
Correspondence to:
Dr P S Thomas, Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW 2031, Australia;
paul.thomas{at}unsw.edu.au

Background: Inhaled tumour necrosis factor alpha (TNF ) 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)TNF 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 TNF, and the exhaled gaseous markers of inflammation, nitric oxide and carbon monoxide.

Results: PC₂₀ showed an increase in sensitivity after TNF 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 TNF , 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 rhTNF indicates that TNF may contribute to the airway inflammation that characterises asthma.

Keywords: asthma; tumour necrosis factor

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