ABSTRACT
BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous disease with various clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA expression patterns in an unselected group of adult asthma patients to characterize the underlying inflammatory process. METHODS: Differential cell counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum from 40 controls and 66 asthmatic adults. A 'cytokine-high' profile was defined if mRNA levels for that particular cytokine exceeded the 90th percentile value in the control population. Radar graphs were used to visualize cytokine profiles. RESULTS: Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among patients. Thirty-six patients (55%) had a Th2 cytokine pattern: 'IL-5-high' (n = 13), 'IL-4-high' (n = 17) or 'IL-4- and IL-5-high' (n = 6). The 'IL-5-high' asthma profile (n = 13) coincided with the 'IL-25-high' (10/13) and surprisingly also with the 'IL-17A-high' (11/13) profile. The 'IL-5-/IL-25-/IL-17A-high profile was different from the 'IL-4-high' pattern. Patients with the 'IL-5, IL-17A, IL-25-high' pattern had significantly worse lung function parameters. Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5, IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P = 0.002; P = 0.066) and uncontrolled asthma is more common among 'IL-5- and IL-17A-high' asthmatics compared to 'IL-5-, IL-17A-low' asthmatics (χ(2) = 3.7, P = 0.027; relative risk (RR): 1.8, 95% CI = 1.1-3.1). CONCLUSIONS AND CLINICAL RELEVANCE: Patients with the 'IL-5, IL-17A, IL-25-high' airway inflammatory pattern are often uncontrolled asthmatics, despite daily treatment. It seems worthwhile to evaluate whether measuring sputum cytokine levels might be used to assess the response to increased doses of steroids in patients with asthma.
Subject(s)
Asthma/genetics , Interleukin-17/genetics , Interleukin-5/genetics , Sputum/chemistry , Adult , Asthma/drug therapy , Asthma/immunology , Case-Control Studies , Cytokines/genetics , Cytokines/immunology , Female , Gene Expression Regulation , Humans , Interleukin-17/immunology , Interleukin-5/immunology , Male , Middle Aged , Risk Factors , Sputum/immunology , Th2 Cells/immunology , Th2 Cells/metabolism , Transcriptome , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The increased susceptibility of asthmatics to rhinovirus infection has recently been related to deficient IFN-lambda 1 (IL-29) and IFN-lambda 2/3 (IL-28) production by bronchial epithelial cells and macrophages. OBJECTIVES: Here, we studied IFN-lambda mRNA expression in the airways of stable asthmatics in comparison with healthy subjects and in relation to asthma symptoms, non-invasive parameters of airway inflammation and lung function parameters. METHODS: Airway cells were obtained by sputum induction, in 14 healthy and 35 asthmatic adults and 12 asthmatic school-aged children. IFN-lambda was studied at the mRNA level by quantitative RT-PCR. RESULTS: Asthmatic adults have increased sputum IL-28 mRNA but similar IL-29 mRNA expression in comparison with healthy subjects. In asthmatics, both sputum IL-28 and IL-29 mRNA expression correlate with the sputum CD3 gamma mRNA expression (reflecting infiltrated T cells). IL-28 (but not IL-29) mRNA levels correlate with the relative and absolute number of eosinophils present in the sputum sample. Sputum IL-29 mRNA (but not IL-28) correlates negatively with asthma symptoms in steroid-naive patients and is significantly higher in steroid-treated than in steroid-naive patients. Finally, both IL-28 and IL-29 mRNA levels are higher in asthmatic children than in asthmatic adults. CONCLUSION: Our results show that asthmatic subjects have substantial type III IFN-lambda mRNA levels in the airways. Our data furthermore suggest that IL-29 could have an immunoprotective role in the lower airways.