通过活体共聚焦显微镜观察细菌性角膜炎患者人泪液细胞因子水平与角膜细胞变化之间的相关性。
Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy.
作者信息
Yamaguchi Takefumi, Calvacanti Bernardo M, Cruzat Andrea, Qazi Yureeda, Ishikawa Shizu, Osuka Akinori, Lederer James, Hamrah Pedram
机构信息
Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
出版信息
Invest Ophthalmol Vis Sci. 2014 Oct 16;55(11):7457-66. doi: 10.1167/iovs.14-15411.
PURPOSE
We investigated bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs).
METHODS
A total of 54 (13 BK, 13 contralateral, 28 healthy controls) tear samples was collected prospectively and analyzed by multiplex microbeads assay. The IVCM of the central cornea was performed on the same day, and assessed for corneal nerve and DC alterations.
RESULTS
Interleukin-1β, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6 ± 26.8, 7174 ± 2430, and 810 ± 315 ρg/mL, respectively; P = 0.04, P < 0.001, and P < 0.001, respectively), compared to healthy controls (13.0 ± 4.0, 171.8 ± 32.1, and 56.5 ± 33.8 ρg/mL). Levels of chemokine ligand 2 (CCL-2), IL-10, and IL-17a were elevated only in contralateral eyes (813 ± 478, 86.7 ± 38.3, and 3350 ± 881 ρg/mL, respectively; P = 0.02, P = 0.01, and P = 0.04, respectively), compared to controls (73.7 ± 25.3, 17.5 ± 4.9, and 1350 ± 337 ρg/mL). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in affected (551 ± 231 ρg/mL, P = 0.02) and contralateral unaffected (545 ± 298 ρg/mL, P = 0.03) eyes compared to controls (31.3 ± 12.4 ρg/mL). The density of DCs was significantly increased in affected (226.9 ± 37.3 cells/mm(2), P < 0.001) and unaffected (122.3 ± 23.7 cells/mm(2), P < 0.001) eyes compared to controls (22.7 ± 5.9 cells/mm(2)). Sub-basal nerve density significantly decreased in affected (3337 ± 1615 μm/mm(2), P < 0.001) and contralateral (13,230 ± 1635 μm/mm(2), P < 0.001) eyes compared to controls (21,200 ± 545 μm/mm(2)). Levels of IL-1β, IL-6, and IL-8 were significantly correlated with DC density (R = 0.40, R = 0.55, and R = 0.31, all P < 0.02) and nerve density (R = -0.30, R = -0.53, and R = -0.39, all P < 0.01).
CONCLUSIONS
Proinflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM.
目的
我们研究了单侧细菌性角膜炎（BK）患者双侧泪液细胞因子水平，并将其与角膜神经和树突状免疫细胞（DCs）的体内共聚焦显微镜（IVCM）改变相关联。
方法
前瞻性收集了54份泪液样本（13例BK患者、13例对侧眼、28例健康对照），并通过多重微珠分析法进行分析。于同一天对中央角膜进行IVCM检查，并评估角膜神经和DCs的改变。
结果
与健康对照（分别为13.0±4.0、171.8±32.1和56.5±33.8μg/mL）相比，白细胞介素-1β、IL-6和IL-8仅在患眼中显著升高（分别为66.6±26.8、7174±2430和810±315μg/mL；P=0.04、P<0.001和P<0.001）。趋化因子配体2（CCL-2）、IL-10和IL-17a水平仅在对侧眼中升高（分别为813±478、86.7±38.3和3350±881μg/mL；P=0.02、P=0.01和P=0.04），与对照（73.7±25.3、17.5±4.9和1350±337μg/mL）相比。与对照（31.3±12.4μg/mL）相比，髓样细胞表达的触发受体（TREM）-1在患眼（551±231μg/mL，P=0.02）和对侧未患眼（545±298μg/mL，P=0.03）中显著升高。与对照（22.7±5.9个细胞/mm²）相比，DCs密度在患眼（226.9±37.3个细胞/mm²，P<0.001）和未患眼（122.3±23.7个细胞/mm²，P<0.001）中显著增加。与对照（21200±545μm/mm²）相比，患眼（3337±1615μm/mm²，P<0.001）和对侧眼（13230±1635μm/mm²，P<0.001）的基底神经密度显著降低。IL-1β、IL-6和IL-8水平与DCs密度（R=0.40、R=0.55和R=0.31，均P<0.02）和神经密度（R=-0.30、R=-0.53和R=-0.39，均P<0.01）显著相关。
结论
单侧BK患者双侧促炎泪液细胞因子升高，且与IVCM检测到的DCs和神经密度改变密切相关。
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