Wegner Alexander, Benson Sven, Rebernik Laura, Spreitzer Ingo, Jäger Marcus, Schedlowski Manfred, Elsenbruch Sigrid, Engler Harald
1 Department of Orthopedics and Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
2 Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Innate Immun. 2017 Jul;23(5):432-439. doi: 10.1177/1753425917707026. Epub 2017 Apr 26.
Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.
临床数据表明，炎症反应存在性别差异，但其机制仍不清楚。在此，我们评估了健康男性和女性体内及体外对细菌内毒素的细胞因子反应，以阐明炎症反应中性别差异背后的全身和细胞因素的作用。参与者接受静脉注射低剂量内毒素（0.4 ng/kg体重），并在6小时内分析血浆TNF-α和IL-6反应。同时，在体内给予内毒素之前立即采集的内毒素刺激血样中测量体外细胞因子产生。由于糖皮质激素（GCs）在炎症反应的负反馈调节中起重要作用，我们还分析了血浆皮质醇浓度和细胞因子产生的体外GC敏感性。结果显示，与男性相比，女性体内的促炎反应更强，血浆TNF-α和IL-6浓度显著升高。此外，内毒素诱导的血浆皮质醇升高在女性中更为明显。相比之下，未观察到体外细胞因子产生和GC敏感性的性别差异。总之，这些发现表明体内和体外对内毒素的反应存在主要差异，并强调了炎症反应中性别差异背后全身因素的重要性。
