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Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

¹ Depts of Respiratory and Sleep Medicine, ³ Cell and Molecular Biology, and ⁴ Immunology and Infectious Diseases, John Hunter Hospital and School of Medical Practice and Population Health, Faculty of Health, University of Newcastle, Newcastle, Australia. ² Respiratory Cell and Molecular Biology, Research Division, Southampton General Hospital, Southampton, UK

CORRESPONDENCE: P.G. Gibson, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, NSW, 2310, Australia. Fax: 61 249213469. E-mail: mdpgg@mail.newcastle.edu.au

Keywords: allergic aspergillosis, asthma, induced sputum, interleukin-8

Received: January 14, 2002
Accepted December 3, 2002

This study was supported by the Asthma Foundation of New South Wales and the National Health and Medical Research Council of Australia.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA.

Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay.

Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second.

Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis.

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