INCREASED EXHALED NITRIC OXIDE ARE CORRELATED WITH TH

INCREASED EXHALED NITRIC OXIDE ARE CORRELATED WITH TH 17 AND SERUM IL-17 IN PERSISTENT ASTHMA Yi-Giien Tsai 1, Jien-Wen Chien 1, Ching-Yuang Lin 2, Kuender D. Yang 3, Jun-Kai Kao 1 1 Departments of Pediatrics, Changhua Christian Hospital, Taiwan 2 Clinical Immunological Center, China Medical 3 University Hospital, Taiwan Department of Medical Research, Show Chwan Memorial Hospital, Taiwan Introduction Measurement of fraction exhaled nitric oxide (Fe. NO) is a simple and noninvasive method for assessment of airway inflammation. IL-17 play an important role in the T celldependent inflammatory response in allergic asthma and it could act as a potent activator of inducible nitric oxide synthase (i. NOS) to amplify Fe. NO. The aim of study was first to evaluate the differences in the Th 17 cells, serum IL 17 and F e N O levels of mild intermittent to severe persistent asthmatics in children. Methods and Materials One hundred asthmatic children divided into the mild intermittent, mild persistent, and moderate to severe persistent groups and 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, Fe. NO levels, CD 4+IL-17 A+ T cells counts from PBMCs, i. NOS production by sputum cells and serum IL-17 levels. Figure 1. Mean fractional exhaled nitric oxide levels in Global Figure 2. serum IL-17 levels in Global Initiative for Asthma guideline-based asthma severity measure groups. (*mean P < 0. 05) Results Serum IL-17 and Fe. NO levels were significantly higher in mild to severe persistent asthmatic patients than in intermittent asthmatics or healthy controls (p < 0. 05). The percentage of CD 4+IL-17 A+ T cells was higher in moderate-to-severe persistent asthmatics than in mild asthmatics (p < 0. 01). Moderate-tosevere asthmatics exhibited greater i. NOS production in sputum cells than mild cases. Decreased i. NOS 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 F e N O, negatively correlated with C-ACT in asthmatics. Figure 3. Associations between serum IL-17 and fractional exhaled nitric oxide in asthmatic children. r: Spearman’s rho correlation coefficient Figure 4. Intracellular IL-17 A in CD 4+ T cells in asthmatic children. Conclusions Th 17 and serum IL-17 are markers of systemic inflammation, in conjunction with augmented Fe. NO, speculating on its biological consequences and possible therapeutic importance in persistent asthmatics. Figure 5. i. NOS expression in sputum cells from asthmatic children. (a) Sputum cells (2 X 106 cells/m. L) were treated with IL-17 neutralizing antibody (40 ng/m. L) for 1 day from mild intermittent asthmatics (n = 5) and moderate to severe asthmatics (n = 5). i. NOS expression was determined by immunoblot-analysis. (b) Statistical data of experiments on paired samples (*P < 0. 05; between mild intermittent and moderate to severe persistent asthmatics). (#P < 0. 05 as compared with IL-17 neutralizing antibody).