%0 Journal Article %A Maysa A Rodrigues Brandao-Rangel %A Renilson Moraes-Ferreira %A Anamei Silva-Reis %A Palmeira H S Palmeira %A Francine M Almeida %A Olimpio R S Olimpio %A Lucas S Zamarioli %A Carlos R Oliveira %A Nilsa R Damaceno-Rodrigues %A João B Pesquero %A Flavio Aimbire %A Rodolfo De Paula Vieira %T Aerobic Exercise Effects in Severe Asthma: Involvement of Lung Fibroblast (MRC-5) Cells and Kinins Signaling %D 2021 %R 10.1183/13993003.congress-2021.PA2331 %J European Respiratory Journal %P PA2331 %V 58 %N suppl 65 %X Bradykinin (Bk) plays a central role in severe asthma, triggering proliferation and activation of lung fibroblasts, resulting in airway remodeling. IL-1beta is released at higher amounts by hyperactivated lung fibroblasts. Aerobic exercise (AE) decreases airway inflammation and remodeling in models of asthma inducing IL-10 release. We tested if AE-induced IL-10 may also reduce severe asthma phenotype in vivo and in vitro (mimicking Bk-induced lung fibroblast proliferation). The in vivo study used (Control, AE, HDM and HDM+AE groups), and an asthma model in C57Bl6 mice [HDM (100ug/mouse, 3x/week, 6 weeks)], treated with AE (5x/week, 4 weeks, beginning after 2nd week of HDM administration). AE reduced eosinophils (p<0.01), neutrophils (p<0.01) and Th1 (p<0.01) and Th2 (p<0.01) cytokines, beyond reducing IL-1beta and increasing IL-10 (p<0.01) in BAL and in plasma. AE reduced HDM-induced airway collagen (p<0.01), mucus (p<0.01) and smooth muscle thickness (p<0.01), resulting in improved airway resistance (RAW, p<0.01), tissue elastance (HTIS, p<0.01) and tissue resistance (GTIS, p<0.01), beyond to reduce the expression (qRT-PCR) of Bk receptor B1 in lung tissue (p<0.01). In addition, in MRC-5 cells (lung fibroblasts), HDM (446,95±70,37 pg/mL; p<0.01), Bk (348,41±17,99 pg/mL; p<0.01) increased IL-1beta release, effects exacerbated when HDM+Bk (814,97±131,52 pg/mL; p<0.001) were associated. On the other side, IL-10, as observed in the in vivo study, almost abolished IL-1beta release [(HDM+Bk 446,95±70,37 pg/mL) vs (HDM+Bk+IL-10 139,22±7,17 pg/mL), p<0.0001]. Aerobic exercise inhibits severe asthma phenotype involving fibroblast deactivation and kinin signaling inhibition.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2331.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). %U