Cytokine mRNA expression in asthma is not restricted to the large airways.
BACKGROUND
Although previous studies have established the presence of an eosinophil-rich cellular infiltrate in the small airways of asthmatic lungs, the expression of cytokines within the peripheral airways has been largely unexplored. The purpose of our study was to test the hypothesis that TH2-type cytokines are increased in the peripheral airways and parenchyma of asthmatic lungs.


METHODS
The presence of messenger ribonucleic acid (mRNA) encoding both T-helper (TH1)-type (IL-2, interferon-gamma) and TH2-type (IL-4, IL-5) cytokines in surgically resected lungs from six asthmatic and 10 nonasthmatic subjects was determined by in situ hybridization. Colocalization of IL-5 mRNA within the large and small airways was performed by simultaneous in situ hybridization and immunocytochemistry.


RESULTS
Expression of IL-5 mRNA-positive cells was significantly increased in the large and small airways and in the lung parenchyma of asthmatic subjects compared with nonasthmatic subjects. In the asthmatic individuals, the expression of IL-5 mRNA was increased in the small airways compared with the large airways. There was also an increase in the number of cells expressing IL-4 mRNA in the large and small asthmatic airways compared with the nonasthmatic airways. In contrast, the numbers of IL-2 and interferon-gamma mRNA-positive cells did not differ between asthmatic and nonasthmatic individuals.


CONCLUSIONS
We conclude that there is an increased expression of TH2-type cytokines within the peripheral airways of asthmatic lungs and suggest that the small airways contribute to the pathophysiology of asthma.
Minshall
E M
EM
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Hogg
J C
JC
Hamid
Q A
QA
D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma