Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression.
BACKGROUND
Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease.


OBJECTIVE
The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition.


METHODS
We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids.


RESULTS
TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens.


CONCLUSIONS
These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.
Chakir
Jamila
J
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Laval, Quebec, Canada.
Shannon
Joanne
J
Molet
Sophie
S
Fukakusa
Motonori
M
Elias
Jack
J
Laviolette
Michel
M
Boulet
Louis-Philippe
LP
Hamid
Qutayba
Q
D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000276:immunology / Q000378:metabolism; D024061:Collagen Type III / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D005355:Fibrosis; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D024022:Fibrillar Collagens; D005938:Glucocorticoids; D017370:Interleukin-11; D020381:Interleukin-17; D016212:Transforming Growth Factor beta; D008775:Methylprednisolone