Sex-related differences in lung inflammation after brain death

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• 作者：Ana Cristina Breithaupt-Faloppa ; PhD^a ; Sueli G. Ferreira ; BS^a ; Guilherme K. Kudo^a ; Roberto Armstrong Jr.^a ; Wothan Tavares-de-Lima ; PhD^b ; Luiz Fernando Ferraz da Silva ; PhD^c ; Paulina Sannomiya ; PhD^a ; Luiz Felipe P. Moreira ; PhD^a ; ^{luiz.moreira@incor.usp.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Brain death ; Sex differences ; Inflammation ; Female sex hormones ; Rat
• 刊名：Journal of Surgical Research
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：200
• 期：2
• 页码：714-721
• 全文大小：910 K

文摘

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.

Materials and 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.