Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1-antitrypsin PiMZ subjects.
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 an increased risk of developing COPD.


METHODS
Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD).


RESULTS
The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (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 changes.
Malerba
M
M
Department of Internal Medicine, University of Brescia, 1st Divisione di Medicina, Spedali Civili, Piazza Spedali Civili 1, 25100 Brescia, Italy. malerba@master.cci.unibs.it
Ricciardolo
F
F
Radaeli
A
A
Torregiani
C
C
Ceriani
L
L
Mori
E
E
Bontempelli
M
M
Tantucci
C
C
Grassi
V
V
D000368:Aged; D001991:Bronchitis / Q000378:metabolism* / Q000473:pathology; D002248:Carbon Monoxide / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D013183:Sputum / Q000166:cytology; D014797:Vital Capacity / Q000502:physiology; D019896:alpha 1-Antitrypsin Deficiency / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D016209:Interleukin-8; D007975:Leukotriene B4; D002248:Carbon Monoxide