Sperry Jason L, Minei Joseph P
Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
J Leukoc Biol. 2008 Mar;83(3):499-506. doi: 10.1189/jlb.0607360. Epub 2007 Sep 25.
Despite ongoing prevention efforts, injury remains the leading cause of mortality over the first three decades of life in the United States. Those who survive their initial injury continue to be plagued with the development of sepsis and multiple organ failure and their attributable morbidity and mortality. An important and persistent finding has been that males and females respond differently following traumatic injury and hemorrhagic shock. A significant advancement in the experimental understanding of the gender dimorphism in response to trauma-hemorrhage and sepsis has occurred. Experimental evidence for the differential effects of sex hormones on cell-mediated immunity and organ system tolerance of shock continues to expand. Clinical studies, however, have been unable to reproduce these laboratory bench findings consistently. There continues to be a divide between the "bench and bedside" in regard to our understanding of gender-based differences following injury. Relative to controlled animal experiments, predisposing comorbidities, injury characteristics, and a lack of information about the hormone milieu of the trauma patient disallow reproducible results from clinical analyses. Continued clinical research into potential sex hormone-based differences, genetic differences, and the cellular and molecular mechanisms responsible for these gender-based differential responses is required to close this gap. This may ultimately promote therapeutic interventions, which will allow for improved outcomes for males and females in the near future.
尽管一直在努力预防,但在美国,受伤仍是30岁前人群死亡的首要原因。那些在初次受伤后幸存下来的人,仍会受到败血症和多器官功能衰竭以及由此导致的发病率和死亡率的困扰。一个重要且持续存在的发现是,男性和女性在创伤性损伤和失血性休克后的反应有所不同。在对创伤性出血和败血症反应中的性别二态性的实验理解方面已经取得了重大进展。性激素对细胞介导免疫和休克器官系统耐受性的不同影响的实验证据不断增加。然而,临床研究一直无法始终如一地重现这些实验室研究结果。在我们对受伤后基于性别的差异的理解方面,“实验室和临床”之间仍然存在差距。相对于对照动物实验,创伤患者的易患合并症、损伤特征以及缺乏关于激素环境的信息,使得临床分析无法得出可重复的结果。需要继续对潜在的基于性激素的差异、基因差异以及导致这些基于性别的差异反应的细胞和分子机制进行临床研究,以弥合这一差距。这最终可能会促进治疗干预,在不久的将来改善男性和女性的治疗效果。