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.