Department of Pulmonology, Allergology and Cystic Fibrosis, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
Shock. 2012 Jul;38(1):37-42. doi: 10.1097/SHK.0b013e3182571e46.
Sex influences the severity and evolution of various inflammatory conditions. Although many studies have demonstrated the role of sex hormones in immune response modulation, recent clinical data revealed significant sex differences in inflammatory markers in prepubertal children, suggesting a genetic contribution. We studied several immune functions depending on X-linked genes in healthy adults of both sexes: the respiratory burst of purified neutrophils, the CD99 and CD11b expression of stimulated leukocytes as markers of adhesion and diapedesis, and the production of inflammatory cytokines in whole blood after incubation with lipopolysaccharide for 24 h. The percentage of monocytes expressing CD99 was higher in men than in women, thus confirming the higher CD99 expression reported in males using reverse transcription-polymerase chain reaction. In addition, we observed a higher tumor necrosis factor α and tendency toward higher interleukin (IL) 6 production in men after lipopolysaccharide stimulation. These differences may contribute to the higher mortality reported in men with septic shock. Tumor necrosis factor α production significantly correlated with monocyte count, with men having a higher monocyte count than women. When cytokine levels were normalized to monocyte counts, a higher IL-8 production was found in women, which may explain the higher neutrophil count observed in girls with acute inflammatory diseases, because IL-8 is a major neutrophil chemoattractant. These sex differences regarding the activation of certain X-linked genes involved in innate immunity confirm our clinical observations, thus supporting the role of sex chromosomes in inflammatory response.
性别会影响各种炎症的严重程度和发展过程。虽然许多研究已经证明了性激素在免疫反应调节中的作用，但最近的临床数据显示，在青春期前儿童中，炎症标志物存在显著的性别差异，这表明遗传因素起到了一定的作用。我们研究了健康成年人中几种依赖 X 连锁基因的免疫功能：纯化中性粒细胞的呼吸爆发、刺激白细胞的 CD99 和 CD11b 表达作为黏附和渗出的标志物，以及在孵育 24 小时后用脂多糖刺激全血产生炎症细胞因子。表达 CD99 的单核细胞百分比在男性中高于女性，从而证实了使用逆转录聚合酶链反应报告的男性中 CD99 表达较高。此外，我们观察到男性在脂多糖刺激后产生的肿瘤坏死因子-α和白细胞介素（IL）6 水平较高。这些差异可能导致男性脓毒性休克的死亡率较高。肿瘤坏死因子-α的产生与单核细胞计数显著相关，男性的单核细胞计数高于女性。当将细胞因子水平与单核细胞计数进行归一化时，发现女性产生的 IL-8 更高，这可以解释为什么在患有急性炎症性疾病的女孩中观察到更高的中性粒细胞计数，因为 IL-8 是一种主要的中性粒细胞趋化因子。这些关于某些参与固有免疫的 X 连锁基因激活的性别差异证实了我们的临床观察结果，从而支持性染色体在炎症反应中的作用。
