Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Cytokine. 2012 Nov;60(2):535-9. doi: 10.1016/j.cyto.2012.07.005. Epub 2012 Jul 28.
In the present investigation, we evaluated the acute changes in intraocular cytokines after intravitreal injection of an anti-vascular endothelial growth factor (VEGF) in diabetic retinopathy (DR). This analysis may contribute to the understanding of changes in intraocular cytokines after intravitreal bevacizumab (IVB), which is frequently used to reduce permeability and neovascularization in DR. This study was a prospective, open-label, controlled, randomized clinical trial. Eyes of 30 consecutive patients who were scheduled for pars plana vitrectomy (PPV) for proliferative DR (PDR) were prospectively enrolled. All patients were randomly assigned to receive IVB either at 1 (group 1) or 7 (group 2) days before PPV, and aqueous humor samples were taken from the anterior chamber just prior to IVB and PPV. The levels of VEGF, interleukin (IL)-2, IL-6, IL-8, tumor necrosis factor (TNF)-α, and transforming growth factor-β(2) (TGF-β(2)) in aqueous humor were evaluated at each time point-baseline and after IVB. VEGF levels were significantly decreased at day 1 (p=0.003) and the decrease sustained through day 7 (p=0.004). IL-6 increased from 23.26 ± 26.68 to 1992.88 ± 2266.87 pg/mL at day 1 (p<0.001) and from 17.13 ± 19.61 to 207.83 ± 269.59 pg/mL at day 7 (p=0.001). IL-6 levels were significantly higher at day 1 compared to day 7 (p=0.002). IL-8 showed an increase at days 1 (p=0.003) and 7 (p=0.002) compared to baseline, with no significant differences between the groups (p=0.157). TGF-β(2) also showed a tendency for an increase at day 7 compared to day 1, but missed statistical significance (p=0.084). No remarkable differences were detected between the 2 groups for IL-2 or for TNF-α at both time points. These results suggest that IVB aggravates intraocular inflammatory cytokines, and IL-6 may mediate those inflammatory changes after IVB in the acute period. These findings also suggest a role for IL-6 as an acute mediator for inflammatory changes in pathologic hypoxic conditions.
在本研究中，我们评估了玻璃体内注射抗血管内皮生长因子（VEGF）治疗糖尿病性视网膜病变（DR）后眼内细胞因子的急性变化。该分析有助于了解玻璃体内贝伐单抗（IVB）治疗后眼内细胞因子的变化，IVB 常用于降低 DR 中的通透性和新生血管形成。本研究为前瞻性、开放标签、对照、随机临床试验。前瞻性纳入了 30 例连续患者，这些患者因增生性糖尿病性视网膜病变（PDR）计划接受玻璃体切除术（PPV）。所有患者随机分为两组，分别于 PPV 前 1 天（第 1 组）或 7 天（第 2 组）接受 IVB，于 IVB 前和 PPV 前从前房采集房水样本。在每个时间点（基线、IVB 后）评估房水中 VEGF、白细胞介素（IL）-2、IL-6、IL-8、肿瘤坏死因子（TNF）-α 和转化生长因子-β（2）（TGF-β（2））的水平。VEGF 水平在第 1 天显著降低（p=0.003），并持续至第 7 天（p=0.004）。IL-6 从 23.26±26.68 增加到第 1 天的 1992.88±2266.87 pg/mL（p<0.001）和第 7 天的 17.13±19.61 增加到 207.83±269.59 pg/mL（p=0.001）。第 1 天的 IL-6 水平明显高于第 7 天（p=0.002）。与基线相比，IL-8 在第 1 天（p=0.003）和第 7 天（p=0.002）均升高，两组之间无显著差异（p=0.157）。TGF-β（2）在第 7 天也有升高的趋势，但未达到统计学意义（p=0.084）。两组在两个时间点的 IL-2 或 TNF-α均无明显差异。这些结果表明，IVB 加重了眼内炎症细胞因子，IL-6 可能在 IVB 后急性炎症期介导这些炎症变化。这些发现还表明，IL-6 可能作为一种急性介质，参与病理性低氧条件下的炎症变化。
