IL-9 and its receptor in allergic and nonallergic lung disease: Increased expression in asthma

Background: Bronchial asthma is a chronic inflammatory disease associated w ith genetic components. Recently IL-9 has been reported as a candidate gene for asthma and to be associated with bronchial hyperresponsiveness and ele vated levels of total serum IgE. Objective: To investigate the contribution of IL-9 to the pathogenesis of a sthma, we examined the expression of IL-9 and its receptor (IL-9R) in bronc hial tissue from subjects with atopic asthma (n = 10), chronic bronchitis ( n = 11), and sarcoidosis (n = 9) and from atopic (n = 7) and nonatopic (n = 10) healthy control subjects. Methods: Bronchial biopsy specimens were examined for the presence of IL-9 and IL-9R protein and messenger RNA (mRNA) by immunocytochemistry and in si tu hybridization, respectively. To phenotype the cells expressing IL-9 in a sthmatic tissue, combined in situ hybridization and immunocytochemistry was also performed. Results: There was a highly significant difference (P < 1.001) in the expre ssion of IL-9 mRNA in asthmatic airways (20.6 +/- 4.0 cells/mm of basement membrane) compared with chronic bronchitis (5.6 +/- 4.4), sarcoidosis (2.5 +/- 1.8), atopic control subjects (7.7 +/- 2.2), and healthy control subjec ts (2.7 +/- 2.3). The number of IL-9 immunoreactive cells was also greater in asthmatic patients compared with the other groups (P < .05). Although th e level of IL-9R mRNA expression did not differ in any of the groups (P > . 05), IL-9R immunoreactivity was significantly higher in asthmatic compared with control subjects. Furthermore, IL-9 mRNA expression levels were also s ignificantly correlated with FEV1 ( P < .05) and the airway responsiveness to methacholine producing a 20% fall in PEV1 (P < .01). The cells expressin g IL-9 mRNA in asthmatic tissue were CD3(+) lymphocytes (68%), major basic protein(+) eosinophils (16%), and elastase(+) neutrophils (8%). Conclusion: The results of this study demonstrate the potential of IL-9 to be a marker for atopic asthma and furthermore suggest an important role for this cytokine in the pathophysiologic mechanisms of this disease.