González Frank, Kirwan John P, Rote Neal S, Minium Judi
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN.
Department of PathoBiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Am J Obstet Gynecol. 2014 Dec;211(6):635.e1-7. doi: 10.1016/j.ajog.2014.06.044. Epub 2014 Jun 20.
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 cells isolated from fasting blood samples and cultured in the presence and absence of LPS. 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 TNF-α and IL-6 release from MNC following LPS exposure was increased (P < .04) in lean and obese women with PCOS and obese controls compared with lean controls. Plasma IL-6 was increased (P < .02) in obese women with PCOS compared with lean women with PCOS, which in turn was increased (P < .02) compared with lean controls. The MNC-derived TNF-α and IL-6 responses from MNCs were negatively correlated with insulin sensitivity (P < .03) and positively correlated with testosterone (P < .03) and androstenedione (P < .006) for the combined groups. Plasma IL-6 was positively correlated with percentage truncal fat (P < .008).
In PCOS, increased cytokine release from MNCs following LPS exposure in the fasting state reveals the presence of MNC 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.
通过检测体外脂多糖（LPS）暴露对空腹状态下细胞因子释放的影响，评估多囊卵巢综合征（PCOS）女性的单核细胞（MNC）预激活情况。
20名PCOS女性（10名瘦型，10名肥胖型）和20名体重匹配的对照者（10名瘦型，10名肥胖型）自愿参与研究。从空腹血样中分离单核细胞，在有和没有LPS的情况下进行培养，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。胰岛素敏感性通过使用松田指数的口服葡萄糖耐量试验得出，躯干脂肪通过双能X线吸收法测量。
与瘦型对照者相比，瘦型和肥胖型PCOS女性及肥胖对照者在LPS暴露后，MNC中TNF-α和IL-6释放相对于基线的变化百分比增加（P < 0.04）。与瘦型PCOS女性相比，肥胖型PCOS女性的血浆IL-6升高（P < 0.02），而与瘦型对照者相比也升高（P < 0.02）。对于合并组，MNC衍生的TNF-α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，空腹状态下LPS暴露后MNC细胞因子释放增加表明存在MNC预激活。重要的是，这种现象与肥胖无关，可能导致PCOS中胰岛素抵抗和高雄激素血症的发生。相比之下，PCOS中血浆IL-6升高的来源可能是过多的脂肪。
