Increased IL-17A secreting CD4+ T cells, serum IL-17 levels and exhaled nitric oxide are correlated with childhood asthma severity

Background Measuring fractional exhaled nitric oxide (FeNO) is a simple and non-invasive method for assessing airway inflammation. IL-17 plays an important role in T cell-dependent inflammatory response that occurs in allergic asthma, it could act as a potent activator of inducible nitric oxide synthase (iNOS) to amplify FeNO levels. Objectives To evaluate the differences in the CD4(+)IL-17A(+) T cell counts, serum IL-17 levels, and FeNO levels in children with mild intermittent to moderate to severe persistent asthma classified by using the Global Initiative for Asthma (GINA). Methods One hundred and twenty asthmatic children divided into the mild intermittent (n=42), mild persistent (n=42), and moderate to severe persistent (n=36) groups, and 20 healthy controls were recruited for the study. Information obtained at visits included the assessment of asthma severity according to GINA guidelines and C-ACT, lung function parameters, FeNO levels, CD4(+)IL-17A(+) T cells counts from PBMCs, iNOS production by sputum cells and serum IL-17 levels. Results Serum IL-17 and FeNO levels were significantly higher in mild to severe persistent asthmatic patients than in intermittent asthmatics or healthy controls (P<0.05). The percentage of CD4(+)IL-17A(+) T cells was higher in moderate to severe persistent asthmatics than in mild asthmatics (P<0.01). Moderate to severe asthmatics (n=5) exhibited greater iNOS production in sputum cells than mild cases (n=5). Decreased iNOS expression in sputum cells was noted in all subjects after IL-17 neutralizing antibody (P<0.05). Serum IL-17 levels were positively correlated with FeNO (rho=0.74; P<0.01), negatively correlated with C-ACT (rho=-0.63; P<0.01) in asthmatics. Conclusion and Clinical Relevance CD4(+) IL-17A(+) T cells counts and serum IL-17 levels in conjunction with augmented FeNO levels are systemic markers of childhood asthma, using these markers, prediction and potential therapeutics for persistent asthmatics may be developed.