Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis
Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis
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DOI：
10.1006/cyto.2001.0861
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发表时间：
2001-05-07
期刊：
影响因子：
3.8
通讯作者：
Chaudry, IH
中科院分区：
文献类型：
--
作者：
Diodato, MD;Knöferl, MW;Chaudry, IH
研究表明，出血后细胞介导的免疫反应存在性别二态性，年轻雄性的反应降低，而发情前期雌性的反应维持或增强。然而，它仍然是未知的性二态免疫反应出血是否提供任何保护，防止随后在体内多微生物败血症的挑战。为了研究这一点，对雄性和发情前期雌性C3 H/HeN小鼠进行出血（35 +/- 5 mmHg持续90分钟，随后进行液体复苏）或假手术。24小时后，通过盲肠结扎和穿孔（CLP）使所有小鼠经受多微生物脓毒症，并在10天的时间段内评估存活率。与假手术相比，CLP前出血显着增加了男性的死亡率。相比之下，假手术组和出血组之间CLP后雌性动物的死亡率相当。在既往出血的男性中，CLP后5小时血浆白细胞介素（IL-）6、肿瘤坏死因子（TNF）-α和前列腺素E-2（PGE（2））水平仅显着增加。相比之下，在这种条件下，雌性动物的IL-6和TNF-α血浆水平没有增加。CLP后雄性和雌性的PGE（2）水平相当，但既往出血显著降低了雌性的PGE（2）水平，而在雄性中未观察到变化。肝、脾组织环氧合酶-2蛋白的表达与血浆PGE的变化密切相关。因此，女性性激素似乎不仅在出血后维持免疫功能方面发挥重要作用，而且在随后的脓毒症挑战中提供生存优势。(C)北京：科学出版社.
Studies have shown gender dimorphism in cell-mediated immune responses following haemorrhage, with depressed responses in young males and maintained or enhanced responses in proestrus females. However, it remains unknown whether or not the sexually dimorphic immune response to haemorrhage provides any protection against a subsequent in vivo polymicrobial septic challenge. To study this, male and proestrus female C3H/HeN mice were subjected to haemorrhage (35 +/- 5 mmHg for 90 min followed by fluid resuscitation) or sham operation. Twenty-four hours thereafter, all mice were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) and survival was assessed over a 10 day period. Haemorrhage prior to CLP significantly increased mortality in males as compared to shams. In contrast, mortality in females following CLP was comparable between the sham and haemorrhage groups. Plasma levels of interleukin (IL-)6, tumour necrosis factor (TNF)-alpha and prostaglandin E-2(PGE(2)) at 5 h after CLP mere significantly increased in males subjected to prior haemorrhage. In contrast, plasma levels of IL-6 and TNF-alpha in females did not increase under such conditions. PGE(2) levels were comparable in males and females following CLP, however prior haemorrhage significantly reduced PGE(2) levels in females, whereas no change was observed in males. Liver and splenic expression of cyclooxygenase-2 protein paralleled the changes in plasma PGE(2). Female sex hormones, therefore, appear to play an important role not only in maintaining immune function following haemorrhage, but also provide a survival advantage against subsequent septic challenge. (C) 2001 Academic Press.