Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 3N9, Canada.
Cells. 2023 Jan 31;12(3):467. doi: 10.3390/cells12030467.
Inflammation is key to the pathogenesis of diabetic retinopathy (DR). This prospective study investigated alterations in inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) in 41 people with type 1 diabetes (T1D), sub-grouped into mild non-proliferative DR (mNPDR; = 13) and active and inactive (each = 14) PDR. Age/gender-matched healthy controls ( = 13) were included. PBMCs were isolated from blood samples. Intracellular cytokine expression by PBMCs after 16-h stimulation (either lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate plus ionomycin, D-glucose or D-mannitol) were assessed by flow cytometry. Cytokine production in plasma, non-stimulated and LPS-stimulated PBMC supernatant was also assessed. Increased BMC IL-10 secretion and reduced expression of IL-6 and IFN-γ in CD3 cells were observed in mNPDR. Reduced IL-6 and IL-10 secretion, and higher levels of intracellular IL-6 expression, especially in CD11b PBMCs, was detected in aPDR; levels were positively correlated with DR duration. Patients with T1D demonstrated increased intracellular expression of IL-17A in myeloid cells and reduced IFN-γ expression in CD3 cells. Plasma levels of IL-1R1 were increased in mNPDR compared with controls. Results suggest that elevated PBMC-released IL-10, IL-6, in particular myeloid-produced IL-17A, may be involved in early stages of DR. IL-6-producing myeloid cells may play a role in PDR development.
炎症是糖尿病视网膜病变 (DR) 发病机制的关键。本前瞻性研究调查了 41 名 1 型糖尿病 (T1D) 患者外周血单个核细胞 (PBMC) 中炎症细胞因子的变化，这些患者分为轻度非增殖性 DR (mNPDR; n = 13) 和活动性和非活动性 (各 n = 14) PDR。纳入了年龄/性别匹配的健康对照者 (n = 13)。从血液样本中分离 PBMC。通过流式细胞术评估 PBMC 在 16 小时刺激后 (脂多糖 (LPS)、佛波醇 12-肉豆蔻酸 13-乙酸酯加离子霉素、D-葡萄糖或 D-甘露醇) 的细胞内细胞因子表达。还评估了血浆、未刺激和 LPS 刺激的 PBMC 上清液中的细胞因子产生。在 mNPDR 中观察到 BMC IL-10 分泌增加和 CD3 细胞中 IL-6 和 IFN-γ 表达减少。在 aPDR 中检测到 IL-6 和 IL-10 分泌减少和细胞内 IL-6 表达水平升高，尤其是在 CD11b PBMC 中，水平与 DR 持续时间呈正相关。T1D 患者在髓样细胞中表现出 IL-17A 的细胞内表达增加，在 CD3 细胞中 IFN-γ 表达减少。与对照组相比，mNPDR 患者的血浆 IL-1R1 水平升高。结果表明，升高的 PBMC 释放的 IL-10、IL-6，特别是髓样细胞产生的 IL-17A，可能参与了 DR 的早期阶段。产生 IL-6 的髓样细胞可能在 PDR 发展中发挥作用。
