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贝伐珠单抗治疗渗出性年龄相关性黄斑变性后房水中的细胞因子谱。

Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration.

机构信息

Department of Ophthalmology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.

Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2023 Sep;261(9):2465-2476. doi: 10.1007/s00417-023-06038-9. Epub 2023 Mar 31.

Abstract

PURPOSE

To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration.

METHODS

Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI -) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay.

RESULTS

C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI - and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI - compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI - group.

CONCLUSION

The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.

摘要

目的

鉴定玻璃体内注射(IVBr)布鲁单抗治疗新生血管性年龄相关性黄斑变性(nAMD)后眼内炎症(IOI)患者房水中的炎症细胞因子谱。

方法

纳入 7 例患者的 8 只眼(IVBrIOI+),这些患者在接受初始 IVBr 后出现 IOI;纳入 16 例患者的 16 只眼(IVBrIOI-),这些患者在接受 IVBr 治疗后未出现 IOI,以及 16 例接受阿柏西普(IVA)治疗的患者作为对照。使用多重免疫分析方法分析房水样本。

结果

IVBrIOI+患者房水中 C-C 基序趋化因子配体(CCL)2、C-X-C 基序趋化因子配体(CXCL)1、CXCL10、CXCL13、白细胞介素(IL)-6、IL-8、IL-10、基质金属蛋白酶(MMP)-1、MMP-9、粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、细胞间黏附分子(ICAM)-1、E 选择素和 P 选择素水平明显高于 IVBrIOI-和 IVA 患者。IVBrIOI-患者房水中血管内皮生长因子(VEGF)水平明显低于 IVBrIOI+和 IVA 患者。在 IVBrIOI+组中,CCL2、CXCL1、IL-6、IL-8、IL-10、G-CSF、GM-CSF、ICAM-1 和 E-选择素之间存在显著相关性,在 IVBrIOI-组中也存在显著相关性。

结论

在 IOI 期间,炎症细胞因子的数量增加,这与 IV 型超敏反应和血管炎症有关。一些细胞因子即使在非炎症眼中也存在相关性,这表明对 IVBr 存在亚临床反应。

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