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玻璃体内注射贝伐单抗对增生型糖尿病视网膜病变患者玻璃体中炎症细胞因子的影响。

Effects of intravitreal injection of bevacizumab on inflammatory cytokines in the vitreous with proliferative diabetic retinopathy.

机构信息

Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

出版信息

Retina. 2014 Jan;34(1):165-71. doi: 10.1097/IAE.0b013e3182979df6.

DOI:10.1097/IAE.0b013e3182979df6
PMID:23851630
Abstract

BACKGROUND

To investigate the effects of preoperative intravitreal injection of bevacizumab (IVB) on the levels of 27 inflammatory cytokines, including interleukins (ILs) and vascular endothelial growth factor.

METHODS

From among 200 patients who had proliferative diabetic retinopathy and underwent vitrectomy in our department from September 2009 to October 2010, 8 study subjects met the enrollment criteria in which both eyes at nearly equivalent stages underwent vitrectomy. The first vitrectomy for each patient was performed without IVB (control group), whereas the second vitrectomy on the contralateral eye was performed with IVB treatment (1.25 mg/0.05 mL) 3 days before surgery (IVB group). Undiluted vitreous fluid was collected at the start of each vitrectomy. A multiplex assay was used to simultaneously determine the levels of 27 inflammatory cytokines and growth factors.

RESULTS

Mean vascular endothelial growth factor levels were significantly lower in the IVB group (519.69 pg/mL) than in the control group (11,807.44 pg/mL) (P = 0.012, Wilcoxon signed rank test). Moreover, the mean levels (IVB/control, pg/mL) of IL-1RA (38.50/62.31, P = 0.036), IL-5 (27.75/34.00, P = 0.018), IL-10 (433.63/1,995.94, P = 0.012), IL-12 (246.69/1,033.69, P = 0.012), IL-13 (707.50/1,450.38, P = 0.012), and interferon γ (71.13/84.69, P = 0.036) were significantly lower in the IVB group. No other significant differences were observed in the levels of the other 20 cytokines and growth factors between the 2 groups.

CONCLUSION

Preoperative IVB reduced not only the intravitreal vascular endothelial growth factor level but also the intravitreal levels of other inflammatory cytokines, including IL-1RA, IL-5, IL-10, IL-12, IL-13, and interferon γ. These results indicate the interaction of some cytokines in the vitreous fluid of proliferative diabetic retinopathy patients and suggest the possibility that preoperative IVB may not only reduce vascular proliferation by its direct antivascular endothelial growth factor effect but also modulate the inflammatory response through putative cytokine networks. None of the other cytokines examined were elevated after IVB.

摘要

背景

研究术前玻璃体内注射贝伐单抗(IVB)对包括白细胞介素(ILs)和血管内皮生长因子在内的 27 种炎症细胞因子水平的影响。

方法

从 2009 年 9 月至 2010 年 10 月在我科接受玻璃体切除术的 200 例增殖性糖尿病视网膜病变患者中,有 8 例符合入选标准的患者,双眼处于相近阶段,均接受玻璃体切除术。每位患者的第一次玻璃体切除术不进行 IVB(对照组),而对侧眼在术前 3 天进行第二次玻璃体切除术,采用 IVB 治疗(1.25mg/0.05mL)(IVB 组)。每次玻璃体切除术开始时收集未稀释的玻璃体液。采用多重检测法同时测定 27 种炎症细胞因子和生长因子的水平。

结果

IVB 组血管内皮生长因子水平(519.69pg/mL)明显低于对照组(11,807.44pg/mL)(P=0.012,Wilcoxon 符号秩检验)。此外,IL-1RA(38.50/62.31,P=0.036)、IL-5(27.75/34.00,P=0.018)、IL-10(433.63/1,995.94,P=0.012)、IL-12(246.69/1,033.69,P=0.012)、IL-13(707.50/1,450.38,P=0.012)和干扰素γ(71.13/84.69,P=0.036)的平均水平在 IVB 组也明显降低。两组间其他 20 种细胞因子和生长因子的水平无其他显著差异。

结论

术前 IVB 不仅降低了眼内血管内皮生长因子水平,而且降低了眼内其他炎症细胞因子的水平,包括 IL-1RA、IL-5、IL-10、IL-12、IL-13 和干扰素γ。这些结果表明,增殖性糖尿病视网膜病变患者玻璃体液中的一些细胞因子相互作用,并提示术前 IVB 不仅可能通过其直接的抗血管内皮生长因子作用来减少血管增殖,还可能通过推测的细胞因子网络来调节炎症反应。IVB 后未检测到其他细胞因子升高。

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