• Fernanda Yamamoto Ricardo-da-Silva, Roberto Armstrong-Jr, Marina Vidal-Dos-Santos, Cristiano de Jesus Correia, Coutinho E SilvaRaphael Dos SantosRDS0000-0001-8818-5043Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paul, Lucas Ferreira da Anunciação, MoreiraLuiz Felipe PinhoLFP0000-0003-0179-4976Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR., Henri Gerrit Derk Leuvenink, and Ana Cristina Breithaupt-Faloppa.
• Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulacao (LIM-11), Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
• Clinics (Sao Paulo). 2021 Jan 1; 76: e3042.

ObjectivesLung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD.MethodsFemale Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed.ResultsEstradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group.ConclusionsBrain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.

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