Differences in airway cytokine profile in severe asthma compared to moderate asthma.
BACKGROUND
Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma.


METHODS
Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry.


RESULTS
Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups.


CONCLUSIONS
Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.
Shannon
Joanne
J
Montreal Chest Institute, Respiratory Division of McGill University Health Centre, Montreal, QC, Canada.
Ernst
Pierre
P
Yamauchi
Yasuhiro
Y
Olivenstein
Ronald
R
Lemiere
Catherine
C
Foley
Susan
S
Cicora
Leo
L
Ludwig
Mara
M
Hamid
Qutayba
Q
Martin
James G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D016207:Cytokines; D016209:Interleukin-8; D007371:Interferon-gamma