title: Sex-related differences in lung inflammation after brain death.
abstract: BACKGROUND
  Donor sex has been suggested to be a factor influencing organ transplantation outcome. Sex hormones possess inflammatory and immune-mediating properties; therefore, immune responses may differ between males and females. Brain death (BD) affects organ function by numerous mechanisms including alterations in hemodynamics, hormonal changes, and increased systemic inflammation. In this study, we investigated sex-dependent differences in the evolution of lung inflammation in a rat model of BD.
  
  
  METHODS
  BD was induced by a sudden increase in intracranial pressure by rapidly inflating a balloon catheter inserted into the intracranial space. Groups of male, female, and ovariectomized (OVx) female rats were used. Lung vascular permeability, inducible nitric oxide synthase, and intercellular adhesion molecule 1 expression were analyzed 6 h after BD. Serum female sex hormones, vascular endothelial growth factor, and cytokine-induced neutrophil chemoattractant 1 levels were also quantified. Lung sections were analyzed by histology.
  
  
  RESULTS
  After 6 h of BD, serum estradiol and progesterone concentrations in female rats were significantly reduced. Lung microvascular permeability was increased in females compared to males. Cytokine-induced neutrophil chemoattractant 1 and vascular endothelial growth factor concentrations were increased in female rats compared to males. Furthermore, female rats showed higher levels of leukocyte infiltration and inducible nitric oxide synthase expression in the lung parenchyma.
  
  
  CONCLUSIONS
  Our results indicate that the more severe lung inflammation in female animals after BD might be related to acute estradiol reduction. Based on our findings, we believe that, in a future study, a group of female treated with estradiol after BD could indicate a possible therapy for the control of lung inflammation in the female donor.
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Sueli G
authors.initials: SG
authors.lastname: Ferreira
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Guilherme K
authors.initials: GK
authors.lastname: Kudo
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Armstrong
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares-de-Lima
authors.affiliation: Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Luiz Fernando Ferraz
authors.initials: LF
authors.lastname: da Silva
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), University of Sao Paulo Medical School, São Paulo, Brazil. Electronic address: luiz.moreira@incor.usp.br.
authors.forename: Luiz Felipe P
authors.initials: LF
authors.lastname: Moreira
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001926:Brain Death / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D009927:Tissue and Organ Procurement
chemical_list: D015415:Biomarkers; D011374:Progesterone; D004958:Estradiol
keywords: Brain death; Female sex hormones; Inflammation; Rat; Sex differences