BACKGROUND: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways.
OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate.
METHODS: Inflammatory cells and IL-17A(+), IL-17F(+), IL-21(+), IL-22(+), and IL-23(+) cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization.
RESULTS: Higher number (P < .05) of neutrophils, IL-17A(+), IL-17F(+), and IL-21(+) cells in bronchial biopsies and higher numbers (P < .01) of IL-17F(+) and IL-21(+) cells in nasal biopsies were observed in SAs compared with MAs. Bronchial IL-17F(+) cells correlated with bronchial neutrophils (r = 0.54), exacerbation rate (r = 0.41), and FEV1 (r = -0.46). Nasal IL-17F(+) cells correlated with bronchial IL-17F (r = 0.35), exacerbation rate (r = 0.47), and FEV1 (r = -0.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4(+)/CD8(+) cells and bronchial/nasal IL-17F(+) cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4(+)/CD8(+) cells.
CONCLUSIONS: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.
- Journal Article