The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-α, interleukin (IL)-6, IL-12, IL-1β, IL-1RA, and IL-10, but not for interferon-γ. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial.

中文翻译：

---

在革兰氏阴性刺激脂多糖的刺激下，男性比女性有更强的单核细胞衍生细胞因子产生反应：一项包括 15 个研究人群的汇总分析。

细菌感染和败血症的发生率以及败血症的死亡风险具有性别特异性。这些临床发现归因于免疫反应的性别差异。本研究的目的是利用 15 个研究人群的细胞因子数据，研究革兰氏阴性刺激脂多糖 (LPS) 刺激后单核细胞衍生的细胞因子产生反应的性别差异。来自这 15 个研究人群的 4,020 名受试者，无论是来自一般人群还是来自患有特定疾病的患者人群，都可以获得全血中 LPS 刺激后体外细胞因子产生反应的个体数据。男性对 LPS 的肿瘤坏死因子-α、白细胞介素 (IL)-6、IL-12、IL-1β、IL-1RA 和 IL-10 的细胞因子产生反应比女性更强，但对干扰素-γ 的细胞因子产生反应则不然。男性的粒细胞-巨噬细胞集落刺激因子产生反应低于女性。这些性别差异与实际年龄无关。由于男性的单核细胞浓度较高，我们将细胞因子产生反应对单核细胞浓度进行标准化。标准化后，LPS对细胞因子产生反应的性别差异消失，但IL-10除外，男性的细胞因子产生反应低于女性。基于性别的方法来解释免疫反应至关重要。