Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1-antitrypsin pimz subjects

MARIO MALERBA ^1*, FABIO RICCIARDOLO ², CHIARA TORREGIANI ¹, ALESSANDRO RADAELI ¹, LUIGI CERIANI ¹, ERICA MORI ¹, MARIO BONTEMPELLI ³, VITTORIO GRASSI ¹ and CLAUDIO TANTUCCI ¹

¹ UNIVERSITY OF BRESCIA, Italy
² IRCCS GASLINI INSTITUTE GENOVA, Italy
³ Ospedali Riuniti di Bergamo, Biochemistry Laboratory, Italy

^* To whom correspondence should be addressed. E-mail: malerba{at}master.cci.unibs.it.

Accepted 30 October 2005

Abstract

Background: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have increased risk of developing COPD.

Methods: The study was aimed to investigate the sputum cell counts and the supernatant level of neutrophil chemoattractant IL-8 by sputum induction in 10 non-smoker asymptomatic PiMZ subjects, with normal pulmonary function, in comparison with 10 stable COPD patients and 10 age-matched normal subjects. Data are expressed as mean ± standard deviation.

Results: In sputum the mean number of neutrophils was significantly higher (p<0.01) in PiMZ (84.5 ± 22.2 x 10⁴/ml), and COPD patients (126,9 ± 18,8 x 10⁴/ml) than in matched normal subjects (55.0 ± 8.7 x 10⁴/ml). IL-8 levels were increased in Pi MZ (828.5 ± 490.6 ng/ml; median 1003.0 ng/ml; range = 1260 - 100 ng/ml), similarly to those found in COPD patients (882.5 ± 524.3 ng/ml; median = 934.9 ng/ml; range = 1506 - 258 mg/ml), compared to normal subjects (3.5 ± 0.5 ng/mL; median = 3.5 ng/ml; range = 4.5 - 2.5 ng/ml). A significant positive correlation between IL-8 supernatant concentration and neutrophils count in PiMZ subjects was found (p=0.036; r=0.66). An inverse correlation between the percentage of neutrophils and FEV1 (% predicted) in COPD patients was observed (p=0.04; r=-0.43).

Conclusions: These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary alterations.

Keywords: COPD, airway inflammation, alpha1-antitrypsin deficiency, induced sputum

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