Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients

• Published in: Thorax Vol. 61; no. 3; pp. 202 - 208
• Main Authors: Truyen, E, Coteur, L, Dilissen, E, Overbergh, L, Dupont, L J, Ceuppens, J L, Bullens, D M A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.03.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; Aged; Allergens; Allergies; ASS; Asthma; Asthma - metabolism; Asthma - physiopathology; asthma symptom score; Biological and medical sciences; Bronchitis - diagnosis; Cells; Chemokines; Chronic obstructive pulmonary disease, asthma; Cytokines; Cytokines - metabolism; eNO; exhaled nitric oxide; Female; FEV1; Forced Expiratory Volume - physiology; forced expiratory volume in 1 second; histamine concentration provoking a 20% decrease in FEV1; Humans; ICS; IFN-γ; induced sputum; Inflammation; inhaled corticosteroids; interferon γ; interleukin; mAb; Male; Medical sciences; messenger RNA; Middle Aged; monoclonal antibody; mRNA; Patients; PC20; Pneumology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; severity; Sputum - metabolism; T helper; Th1 Cells - metabolism; Th1/Th2 cytokines; Th2 Cells - metabolism; Belgium; United States > US; Europe; Human; Measurement; Lung disease; Evaluation; Respiratory disease; Cytokine; Th1 lymphocyte; Cardiovascular disease; Patient; Inflammation; Asthma; Messenger RNA; Immunological investigation; Sputum; T-Lymphocyte; Bronchus disease; Th2 lymphocyte; Obstructive pulmonary disease; Quantitative analysis
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2005.052399

Background: Asthma is a chronic inflammatory disorder of the airways driven by T cell activation. Th2 cells and their cytokines are thought to play a role in the pathophysiology of allergic as well as non-allergic asthma. Methods: Airway cells were obtained by sputum induction from 15 healthy and 39 asthmatic individuals and the airway T cell cytokine profiles (interleukin (IL)-4, IL-5, IL-13, IL-10 and interferon (IFN)-γ) at the mRNA level were studied by real time RT-PCR. Results: Asthma patients had increased expression of IL-5 (p = 0.001) and IL-13 (p = 0.03) mRNA in sputum compared with non-asthmatic controls. IL-4 mRNA and IFN-γ mRNA were detectable in the sputum of 44% and 21% of patients, respectively, but not in controls. Sputum IL-10 mRNA levels did not differ significantly between patients and controls. Sputum mRNA expression levels of IL-4, IL-5, and IL-13 were significantly correlated with the percentage of eosinophils and were higher in subjects with allergic asthma than in those with non-allergic asthma (p = 0.03, p = 0.02 and p = 0.0002, respectively); they did not differ between mild asthmatic subjects and those with moderate to severe asthma. In contrast, IFN-γ mRNA expression was higher in non-allergic than in allergic patients (p = 0.04) and higher in patients with moderate to severe asthma than in those with mild asthma (p<0.01). Sputum IL-5 mRNA levels (but not the other cytokine mRNA levels) were also correlated with exhaled nitric oxide (eNO) and with bronchial hyperreactivity expressed as the histamine concentration resulting in a 20% decrease in forced expiratory volume in 1 second. Conclusion: Real time RT-PCR analysis of mRNA in induced sputum confirms a predominance of Th2 cytokines in both allergic and non-allergic asthma. IL-5 levels reflect eosinophil infiltration as well as eNO levels and hyperreactivity, and levels of the Th1 cytokine IFN-γ indicate asthma severity. The technique is a promising tool for use in further studies of asthma severity and disease activity.