Evidence of mononuclear cell preactivation in the fasting state in polycystic ovary syndrome.

Evidence of mononuclear cell preactivation in the fasting state in polycystic ovary syndrome.
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DOI:
10.1016/j.ajog.2014.06.044
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发表时间:
2014-12
影响因子:
9.8
通讯作者:
Minium, Judi
Minium, Judi
中科院分区:
医学1区
文献类型:
--
作者:
Gonzalez, Frank;Kirwan, John P.;Rote, Neal S.;Minium, Judi

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我们通过检查体外脂多糖 (LPS) 暴露对禁食状态下细胞因子释放的影响,评估了多囊卵巢综合症 (PCOS) 女性的单核细胞 (MNC) 预激活。 20 名患有 PCOS 的女性(10 名瘦,10 名肥胖)和 20 名体重匹配的对照者(10 名瘦,10 名肥胖)自愿参与研究。从空腹血样中分离并在存在和不存在脂多糖的情况下培养的单核细胞中测量肿瘤坏死因子-α (TNF α) 和白细胞介素-6 (IL-6) 的释放。从相同的空腹血样中测量血浆 IL-6。胰岛素敏感性源自使用松田指数的口服葡萄糖耐量测试,并且通过双能X射线吸收测定法测量躯干脂肪。与瘦对照相比,患有 PCOS 的瘦和肥胖女性以及肥胖对照者在暴露于脂多糖后,单核细胞释放的 TNFα 和 IL-6 相对于基线的百分比变化有所增加(皮塔利克>0.04)。与瘦 PCOS 女性相比,肥胖 PCOS 女性的血浆 IL-6 升高 (pbold>0.02),而与瘦对照组相比,血浆 IL-6 也升高 (p<0.02)。对于联合组,单核细胞衍生的 TNFα 和 IL-6 反应与胰岛素敏感性呈负相关 (p<0.03),与睾酮 (p<0.03) 和雄烯二酮 (p<0.006) 呈正相关。血浆 IL-6 与躯干脂肪百分比呈正相关 (p<0.008)。在 PCOS 中,禁食状态下暴露于脂多糖后单核细胞释放的细胞因子增加,揭示了单核细胞预激活的存在。重要的是,这种现象与肥胖无关,并且可能导致多囊卵巢综合征中胰岛素抵抗和雄激素过多症的发生。相反,PCOS 患者血浆 IL-6 升高的原因可能是过度肥胖。
We evaluated mononuclear cell (MNC) preactivation in women with Polycystic Ovary Syndrome (PCOS) by examining the effect of in vitro lipopolysaccharide (LPS) exposure on cytokine release in the fasting state. Twenty women with PCOS (10 lean, 10 obese) and 20 weight-matched controls (10 lean, 10 obese) volunteered for study participation. Tumor necrosis factor-α (TNF α) and interleukin-6 (IL-6) release was measured from mononuclear cell isolated from fasting blood samples and cultured in the presence and absence of lipopolysaccharide. Plasma IL-6 was measured from the same fasting blood samples. Insulin sensitivity was derived from an oral glucose tolerance test using the Matsuda index and truncal fat was measured by dual energy x-ray absorptiometry. The percent change from baseline in TNFα and IL-6 release from mononuclear cell following lipopolysaccharide exposure was increased (pitalic>0.04) in lean and obese women with PCOS and obese controls compared with lean controls. Plasma IL-6 was increased (pbold>0.02) in obese women with PCOS compared with lean women with PCOS, which in turn was increased (p<0.02) compared with lean controls. The mononuclear cell -derived TNFα and IL-6 responses from mononuclear cell were negatively correlated with insulin sensitivity (p<0.03) and positively correlated with testosterone (p<0.03) and androstenedione (p<0.006) for the combined groups. Plasma IL-6 was positively correlated with percent truncal fat (p<0.008). In PCOS, increased cytokine release from mononuclear cell following lipopolysaccharide exposure in the fasting state reveals the presence of mononuclear cell preactivation. Importantly, this phenomenon is independent of obesity and may contribute to the development of insulin resistance and hyperandrogenism in PCOS. In contrast, the source of plasma IL-6 elevations in PCOS may be excess adiposity.
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