Department of Health Promotion Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Invest Ophthalmol Vis Sci. 2012 Aug 13;53(9):5443-50. doi: 10.1167/iovs.11-9417.
To determine cytokine and chemokine concentrations in the tears of patients with dry eye disease (DED) and analyze the possible relationships with the clinical severity of DED.
Patients were examined using the Ocular Surface Disease Index, corneal and conjunctival staining, tear breakup time, and impression cytology. They were divided into four groups according to the Dry Eye Workshop severity classification. Tears were collected from 133 patients with DED and 70 healthy controls. Concentrations of cytokines, chemokines, and soluble receptors in collected tear samples were analyzed using current technology with a Human Cytokine/Chemokine kit, a Human Cytokine/Chemokine Panel, and a Human Soluble Cytokine Receptor Panel.
The levels of cytokines interleukin (IL)-1β (P < 0.05), IL-6 (P < 0.001), IL-16 (P < 0.001), IL-33 (P < 0.05), G-CSF (P < 0.001), and transforming growth factor (TGF)-α (P < 0.05) were significantly higher in patients with DED, whereas those of cytokines IL-4 (P < 0.001), IL-12 (p40) (P < 0.001), IL-17A (P < 0.05), and interferon-γ (P < 0.001) were significantly lower. The levels of Fractalkine (chemokine [C-X3-C motif] ligand 1; CX3CL1), MCP-1 (chemokine [C-C motif] ligand 2; CCL2), MIP-1δ (chemokine [C-C motif] ligand 15; CCL15), and ENA-78 (chemokine [C-X-C motif] ligand 5; CXCL5) (P < 0.001, respectively) and soluble receptors, sIL-1RI (P < 0.05), soluble glycoprotein (sgp) 130 (P < 0.05), sIL-6R (P < 0.001), soluble epidermal growth factor receptor (P < 0.05), and soluble tumor necrosis factor receptor 2 (P < 0.001), were higher in patients with DED. There were significant correlations between these molecules and the clinical severity of DED.
Fifteen molecules were elevated in the tears of patients with DED; four molecules were decreased. Although the levels of sIL-6R, sIL-6R, and sgp130 may be potential indicators of the homeostatic process, an increase in the levels of IL-6 and IL-1 β are the earliest observable changes in patients with DED. Further study on the biomarkers in the pathogenesis of DED and treatment target modalities would be needed.
测定干眼症（DED）患者泪液中的细胞因子和趋化因子浓度，并分析其与 DED 临床严重程度的可能关系。
使用眼表面疾病指数、角膜和结膜染色、泪膜破裂时间和印迹细胞学对患者进行检查。根据干眼工作会议严重程度分类，将患者分为四组。收集 133 例 DED 患者和 70 例健康对照者的泪液。使用人细胞因子/趋化因子试剂盒、人细胞因子/趋化因子面板和人可溶性细胞因子受体面板，利用当前技术分析收集的泪液样本中细胞因子、趋化因子和可溶性受体的浓度。
DED 患者的细胞因子白细胞介素（IL）-1β（P < 0.05）、IL-6（P < 0.001）、IL-16（P < 0.001）、IL-33（P < 0.05）、粒细胞集落刺激因子（G-CSF）（P < 0.001）和转化生长因子（TGF）-α（P < 0.05）水平明显升高，而细胞因子 IL-4（P < 0.001）、IL-12（p40）（P < 0.001）、IL-17A（P < 0.05）和干扰素-γ（P < 0.001）水平明显降低。趋化因子（C-X3-C 基元）配体 1（Fractalkine；CX3CL1）、趋化因子（C-C 基元）配体 2（MCP-1；CCL2）、趋化因子（C-C 基元）配体 15（MIP-1δ；CCL15）和趋化因子（C-X-C 基元）配体 5（ENA-78；CXCL5）（分别为 P < 0.001）以及可溶性受体可溶性白细胞介素 1 受体 I（sIL-1RI）（P < 0.05）、可溶性糖蛋白 130（sgp130）（P < 0.05）、可溶性白细胞介素 6 受体（sIL-6R）（P < 0.001）、可溶性表皮生长因子受体（P < 0.05）和可溶性肿瘤坏死因子受体 2（P < 0.001）在 DED 患者中的水平均升高。这些分子与 DED 的临床严重程度之间存在显著相关性。
DED 患者的泪液中升高了 15 种分子；4 种分子降低。尽管 sIL-6R、sgp130 和 sIL-6R 的水平可能是内稳态过程的潜在指标，但 IL-6 和 IL-1β 的升高是 DED 患者最早观察到的变化。需要进一步研究 DED 发病机制中的生物标志物和治疗靶标模式。
