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玻璃体内雷珠单抗治疗与糖尿病黄斑水肿患者血清细胞因子浓度的关系。

The association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema.

机构信息

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Victoria, Australia.

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

出版信息

Mol Vis. 2020 Apr 1;26:246-256. eCollection 2020.

Abstract

AIM

To investigate the association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema (DME).

METHODS

Twenty-five patients with center-involved DME were recruited prospectively. Serum samples were collected from the patients before and 4 weeks after two ranibizumab injections. The levels of 32 cytokines at these two time points were assessed using a multiplex array assay.

RESULTS

Following two ranibizumab injections, there was a statistically significant decrease in the median [interquartile range] levels of Interleukin 1-1beta (IL-1β) from 5.56 [3.6, 8.75] to 2.33 [1.51, 2.89], Interleukin 13 (IL-13) from 4.30 [1.84, 18.55] to 0.38 [0.38, 0.78], granulocyte-colony stimulating factor (G-CSF) from 64.65 [42.9, 108] to 37.8 [27.3, 46.37], Interferon gamma (IFN-γ) from 241 [103.33, 753.4] to 94.4626 [42.04, 118.58], Interferon gamma-induced protein 10 (IP-10) from 234.68 [144.16, 285.98] to 158.73 [94.71, 198.64], Macrophage Inflammatory Protein-1 alpha (MIP-1α) from 3.65 [2.62, 11.02] to 1.41 [0.94, 1.88], and Tumor necrosis factor- alpha (TNF-α) from 131.09 [100.68,28 240.27] to 45.19 [24.04, 68.55]. There was a statistically significant increase in the levels of Interleukin 9 (IL-9) from 0.76 [0.76, 7.03] to 19.67 [5.36 27.76], Macrophage Inflammatory Protein-1 beta (MIP-1β) from 0.28 [0.28, 30 0.28] to 6.79 [I3.74, 14.16], Vascular endothelial growth factor (VEGF) from 2.55 [2.55, 2.55] to 25.24 [14.51, 41.73], and soluble vascular endothelial growth factor -1 (sVEGFR-1) from 333.92 [204.99, 440.43] to 500.12 [38.7, 786.91]. A Bonferroni-corrected p value of 0.00156 was considered statistically significant.

CONCLUSIONS

In patients with DME, intravitreal ranibizumab therapy appears to influence the serum levels of a range of cytokines. After two injections, intravitreal ranibizumab therapy appears to be associated with a significant decrease in inflammatory mediators and a rise in VEGF and sVEGFR1.

摘要

目的

探讨玻璃体内雷珠单抗治疗与糖尿病黄斑水肿(DME)患者血清细胞因子浓度之间的关系。

方法

前瞻性招募 25 例中心性 DME 患者。在两次雷珠单抗注射前和 4 周后采集患者的血清样本。使用多重微阵列分析评估这两个时间点的 32 种细胞因子的水平。

结果

两次雷珠单抗注射后,白细胞介素 1-β(IL-1β)中位数[四分位距]从 5.56 [3.6,8.75]降至 2.33 [1.51,2.89],白细胞介素 13(IL-13)从 4.30 [1.84,18.55]降至 0.38 [0.38,0.78],粒细胞集落刺激因子(G-CSF)从 64.65 [42.9,108]降至 37.8 [27.3,46.37],干扰素 γ(IFN-γ)从 241 [103.33,753.4]降至 94.4626 [42.04,118.58],干扰素诱导蛋白 10(IP-10)从 234.68 [144.16,285.98]降至 158.73 [94.71,198.64],巨噬细胞炎性蛋白-1α(MIP-1α)从 3.65 [2.62,11.02]降至 1.41 [0.94,1.88],肿瘤坏死因子-α(TNF-α)从 131.09 [100.68,28240.27]降至 45.19 [24.04,68.55]。白细胞介素 9(IL-9)水平从 0.76 [0.76,7.03]升至 19.67 [5.3627.76],巨噬细胞炎性蛋白 1β(MIP-1β)从 0.28 [0.28,300.28]升至 6.79 [I3.74,14.16],血管内皮生长因子(VEGF)从 2.55 [2.55,2.55]升至 25.24 [14.51,41.73],可溶性血管内皮生长因子受体-1(sVEGFR-1)从 333.92 [204.99,440.43]升至 500.12 [38.7,786.91]。经过 Bonferroni 校正后,p 值为 0.00156,认为具有统计学意义。

结论

在 DME 患者中,玻璃体内雷珠单抗治疗似乎会影响一系列细胞因子的血清水平。两次注射后,玻璃体内雷珠单抗治疗似乎与炎症介质的显著减少以及 VEGF 和 sVEGFR1 的升高有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2487/7127926/470033250e1c/mv-v26-246-f1.jpg

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