Abstract
Background: Th-2 cytokine milieu including interleukin 4 (IL-4) was detected in fibrotic lung diseases. Chronic extrinsic allergic alveolitis (EAA) may be also accompanied by marked fibrogenesis. The aim of this study was to determine if IL-4 and its receptor (IL-4R-alpha) play any role in the clinical presentation and pathogenesis of chronic EAA. Methods: Twenty patients originally investigated for interstitial lung disease and finally diagnosed affected with chronic EAA and sarcoidosis were prospectively enrolled into the study. Concentrations of IL-4, IL-4R-aplha and total protein were assessed in the bronchoalveolar lavage fluid (BALF) of all enrolled subjects as well as high resolution computed tomography (HRCT) scores and pulmonary function tests. Results: BALF IL-4R-alpha and total protein concentrations were significantly higher in chronic EAA patients (p < 0.05). Concentrations of BALF IL-4R-alpha were significantly higher in men than in women (p < 0.05) in EAA group. Total protein BALF levels were significantly elevated in ex-smokers with EAA compared to nonsmokers (p < 0.05). A positive correlation (p < 0.01) between IL-4R-alpha BALF concentrations and HRCT interstitial scores were observed in chronic EAA group; the IL-4R-alpha/total protein ratio showed the same significant positive correlation. A negative correlation between lung function results and IL-4R-alpha, and IL-4R-alpha/total protein as well, was also found (p < 0.05). Conclusions: We suggest a clinical relevance for the IL-4/IL-4R axis in the etiopathogenesis of chronic EAA. IL-4R-alpha could serve as a potential biomarker of lung fibrogenesis.
Highlights
Th-2 cytokine milieu including interleukin 4 (IL-4) was detected in fibrotic lung diseases
Sarcoidosis is considered to be a typical Th1 disease, studies of IL-4 receptors (IL-4R) gene polymorphisms have showed no association with sarcoidosis, and no differences were found in IL-4 bronchoalveolar lavage fluid (BALF) concentrations from sarcoidosis patients compared to healthy controls [10,11]
The second aim of this study was to determine if an association between IL-4/IL-4R-alpha and extrinsic allergic alveolitis (EAA) etiopathogenesis could be supported by a correlation between BALF concentrations and the clinical presentation of the disease (i.e., BALF differential cell count, pulmonary function tests and high resolution computed tomography (HRCT) scores)
Summary
Th-2 cytokine milieu including interleukin 4 (IL-4) was detected in fibrotic lung diseases. Chronic extrinsic allergic alveolitis (EAA) may be accompanied by marked fibrogenesis. The aim of this study was to determine if IL-4 and its receptor (IL-4R-alpha) play any role in the clinical presentation and pathogenesis of chronic EAA. Th2 cytokine milieu was found to play a role in the etiopathogenesis of pulmonary fibrosis in chronic EAA patients [3]. Interleukin-4 (IL-4) is a Th2 cytokine and has been found to take part in the pathogenesis of fibrosis in the ‘bleomycin model,’ as well as in idiopathic pulmonary fibrosis (IPF) patients. Despite pulmonary fibrosis is the main histopathological and radiological feature of chronic EAA, the role of IL-4 and IL-4R in EAA pathogenesis has not been studied yet
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