Department of Biology, University of Turku, Finland.
J Diabetes Complications. 2011 Nov-Dec;25(6):393-7. doi: 10.1016/j.jdiacomp.2011.06.002. Epub 2011 Aug 2.
The purpose was to assess the activity of nuclear factor (NF)-κB and hypoxia inducible factor (HIF)-1α transcription factors and the expression levels of inflammation markers [interleukin (IL)-6 and IL-8] in the vitreous of patients suffering from proliferative diabetic retinopathy (PDR) scheduled for elective vitreous surgery in a single academic-based retina practice in a prospective clinical study.
Twenty-seven patients with PDR were enrolled in the study. The severity of retinopathy was classified (0, 1, 2, 3, 4) and the activity of neovascularization was graded (0, 1, 2, 3, 4) by the surgeon intraoperatively. Samples of the vitreous were collected during surgery, and the activity of NF-κB and HIF-1α transcription factors and the expression levels of IL-6 and IL-8 were measured.
The majority of samples fell into the retinopathy class 3 (n = 12) or 4 (n = 13). The level of IL-6 increased from 68.9 ± 46.8 pg/ml to 102.7 ± 94.1 pg/ml, and IL-8 increased from 165.1 ± 136.0 pg/ml to 521.0 ± 870.9 pg/ml (mean ± S.D., nonsignificant change: normality test followed with Mann-Whitney Rank Sum Test). According to the neovascularization activity, the samples fell into grade 1 (n = 7), 2 (n = 12) or 3 (n = 7). In IL-6, there was a statistically significant increase (P < .05) from grade 2 to 3: 58.6 ± 40.3 pg/ml and 158.4 ± 102.5 pg/ml, respectively (Kruskal-Wallis One-Way Analysis of Variance on Ranks followed with Dunn's Method). The level of IL-8 was as follows: in grade 1: 118.0 ± 62.4 pg/ml, in grade 2: 192.3 ± 127.1 pg/ml and in grade 3: 884.3 ± 1161.0 pg/ml (statistically nonsignificant change). There was a statistically significant linear regression between IL-6 and IL-8 (P < .001): IL-6 = 51.88 pg/ml + (0.092*IL-8), r = 0.772. Increased activity of the NF-κB and HIF-1α transcription factors was not observed.
Interleukin-6 is a candidate to indicate activity of neovascularization process in PDR. It might be a new molecular therapeutic target to regulate innate immunity response in vitreous.
评估核因子 (NF)-κB 和缺氧诱导因子 (HIF)-1α 转录因子的活性以及炎症标志物[白细胞介素 (IL)-6 和 IL-8]在接受择期玻璃体手术的增殖性糖尿病视网膜病变 (PDR)患者玻璃体中的表达水平，这是在一个学术性视网膜实践中进行的前瞻性临床研究。
研究纳入 27 例 PDR 患者。手术中由外科医生对视网膜病变严重程度进行分级（0、1、2、3、4），新生血管活动度进行分级（0、1、2、3、4）。术中采集玻璃体样本，测量 NF-κB 和 HIF-1α 转录因子的活性以及 IL-6 和 IL-8 的表达水平。
大多数样本属于视网膜病变 3 级（n=12）或 4 级（n=13）。IL-6 水平从 68.9±46.8pg/ml 升高至 102.7±94.1pg/ml，IL-8 水平从 165.1±136.0pg/ml 升高至 521.0±870.9pg/ml（平均值±标准差，无显著变化：正态性检验后采用 Mann-Whitney 秩和检验）。根据新生血管活动度，样本分为 1 级（n=7）、2 级（n=12）或 3 级（n=7）。IL-6 从 2 级到 3 级有统计学显著升高（P<.05）：分别为 58.6±40.3pg/ml 和 158.4±102.5pg/ml（Kruskal-Wallis 单向方差分析秩次检验后采用 Dunn 法）。IL-8 水平如下：1 级：118.0±62.4pg/ml，2 级：192.3±127.1pg/ml，3 级：884.3±1161.0pg/ml（无统计学显著变化）。IL-6 和 IL-8 之间存在统计学显著线性回归（P<.001）：IL-6=51.88pg/ml+（0.092*IL-8），r=0.772。未观察到 NF-κB 和 HIF-1α 转录因子活性的增加。
白细胞介素-6 可能是 PDR 新生血管化过程活性的候选标志物。它可能成为调节玻璃体固有免疫反应的新的分子治疗靶点。
