IL-11 expression is increased in severe asthma: association with epithelial cells and eosinophils.
BACKGROUND
IL-11 is a pleiotropic cytokine produced by a variety of stromal cells. Targeted overexpression of this cytokine in mice results in a remodeling of the airways and the development of airway hyperresponsiveness and airway obstruction.


OBJECTIVE
Because these alterations mimic important pathologic and physiologic changes in the airways of some asthmatic patients, we investigated the expression of IL-11 messenger RNA (mRNA) within the airways of patients with mild to severe asthma and nonasthmatic control subjects.


METHODS
Fiberoptic bronchoscopy to obtain bronchial biopsy specimens was performed on patients with mild (n = 13), moderate (n = 10), and severe (n = 9) asthma and on nonasthmatic control subjects (n = 9).


RESULTS
These patients differed in their extent of airway fibrosis with types I and III collagens being noted in greater quantities in the biopsy specimens from the severe and moderate asthmatics than in those from controls (P <.05). IL-11 mRNA expression was observed in the epithelial and subepithelial layers of asthmatic and nonasthmatic control subjects. The number of cells within the epithelium and subepithelium expressing IL-11 mRNA was greater in those with moderate and severe asthma compared with mild asthma and nonasthmatic subjects (P <.001). There were also greater numbers of IL-11 mRNA-positive cells within the subepithelium in severe compared with moderate asthma (P <.001). Immunostaining for IL-11 within the airway tissues confirmed translation of the mRNA into IL-11-immunoreactive protein in airway epithelial cells. Colocalization of IL-11 mRNA and immunoreactivity with resident inflammatory cells demonstrated that this cytokine was also expressed by major basic protein-positive eosinophils.


CONCLUSIONS
These results suggest that IL-11 is involved in the chronic remodeling seen in asthmatic airways and is associated with increasing severity of the disease.
Minshall
E
E
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Chakir
J
J
Laviolette
M
M
Molet
S
S
Zhu
Z
Z
Olivenstein
R
R
Elias
J A
JA
Hamid
Q
Q
D001249:Asthma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017370:Interleukin-11 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012260:Ribonucleases; D013194:Staining and Labeling
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D017370:Interleukin-11; D012333:RNA, Messenger; D003094:Collagen; D012260:Ribonucleases