AUTHOR=Sierra Ana Paula Renno , Martínez Galán Bryan Steve , de Sousa Cesar Augustus Zocoler , de Menezes Duane Cardoso , Branquinho Jéssica Laís de Oliveira , Neves Raquel Leão , Arata Júlia Galanakis , Bittencourt Clarissa Azevedo , Barbeiro Hermes Vieira , de Souza Heraldo Possolo , Pesquero João Bosco , Cury-Boaventura Maria Fernanda TITLE=Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms JOURNAL=Frontiers in Physiology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.919544 DOI=10.3389/fphys.2022.919544 ISSN=1664-042X ABSTRACT=Renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) have a different site of interaction and modulate vascular tone and inflammatory response as well on exercise adaptation, which is modulated by exercise-induced cytokines. The aim of the study was to evaluate the role of ACE I/D and BDKRB2 +9/-9 polymorphism on exercise-induced cytokine response. Seventy-four male marathon finishers, aged 30 to 55 years, participated in this study. Plasma levels of exercise-induced cytokines were determined 24 h before, immediately after, and 24 h and 72 h after the São Paulo International Marathon. Plasma concentrations of MCP-1, IL-6 and FGF-21 increased after marathon in all genotypes of BDKRB2. IL-10, FSTL and BDNF increased significantly after marathon in the genotypes with the presence of the -9 allele and IL-8, FSTL and BDNF concentrations were higher in the -9/-9 genotype compared to the +9/+9 genotype before and after the race, respectively. Apelin, IL-15, musclin and myostatin concentrations were significantly reduced after the race only in the presence of -9 allele. Marathon increased plasma concentrations of MCP1, IL-6, BDNF and FGF-21 in all genotypes of ACE I/D polymorphism. Plasma concentrations of IL-8, MIP-1alpha and TNF-alpha before the race; MIP-1alpha and TNF-a levels after the marathon race and VEGF levels 72 h after the race were lower in DD compared to ID runners. Before the marathon race myostatin concentrations were higher in DD compared to II genotypes. Myostatin, musclin, IL-15, IL-6 and apelin levels decreased after race in genotypes with the presence of D allele. The runners with the -9/-9 genotype have greater response in exercise-induced cytokines related to muscle repair and cardioprotection indicating that BDKRB2 participate on exercise adaptations and runners with DD genotype have anti-inflammatory response as well as ACE activity was positively correlated with anti-inflammatory mediators. DD homozygotes also had higher myostatin levels which modulates protein homeostasis.