Leonardi Andrea, Jose Peter J, Zhan Hong, Calder Virginia L
Department of Ophthalmology, University of Padua, via Foscari 8, 35127 Padua, Italy.
Ophthalmology. 2003 Mar;110(3):487-92. doi: 10.1016/S0161-6420(02)01767-0.
Eotaxin-1 and eotaxin-2 are potent eosinophil chemotactic and activating peptides that may be implicated in the pathogenesis of the chronic allergic eye diseases vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The purpose of this study was to measure these chemokines in tear and mucus samples of active-disease patients and in vitro cultured conjunctival epithelial cells and fibroblasts.
Comparative, observational case series and in vitro study.
Sixteen patients with clinically active and untreated VKC or AKC, six age-matched control patients, and five nonactive seasonal allergic conjunctivitis patients.
Tears were collected from the active VKC and AKC patients, and from the normal patients. Mucus was collected from six of these VKC patients. Tears were also collected from an additional five allergic patients after obtaining a positive reaction to conjunctival allergen challenge. Conjunctival epithelial cell and conjunctival fibroblast cultures were exposed to interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-alpha), or to combinations of these cytokines.
Levels of eotaxin-1 and eotaxin-2 in tears, mucus, and culture medium.
High levels of eotaxin-1 and eotaxin-2 were found in mucus of VKC patients, whereas only eotaxin-2 was found to have increased significantly in tears of VKC and AKC patients compared with those of normal patients. Mucus contained higher levels of chemokines than did tears. Both tear eotaxin-1 and eotaxin-2 were correlated significantly with the percent of eosinophils in tear fluid. Eotaxin-1 also was correlated significantly with the sum clinical score and corneal involvement in VKC patients. Conjunctival epithelial cells in culture did not produce eotaxin-1 or eotaxin-2, either at baseline or after cytokine exposure. Conjunctival fibroblasts produced eotaxin-1 only after exposure to IL-4, TNF-alpha, and the combination of IL-4 plus TNF-alpha or IL-13 plus TNF-alpha.
Eotaxin-1 and eotaxin-2 are implicated in eosinophil recruitment and in the pathogenesis of VKC and AKC. Cytokine-stimulated conjunctival fibroblasts may be one source of eotaxin-1 in severely allergic tissues.
嗜酸性粒细胞趋化因子-1和嗜酸性粒细胞趋化因子-2是强效的嗜酸性粒细胞趋化和激活肽，可能与慢性变应性眼病春季角结膜炎（VKC）和特应性角结膜炎（AKC）的发病机制有关。本研究的目的是检测活动性疾病患者的泪液和黏液样本以及体外培养的结膜上皮细胞和成纤维细胞中的这些趋化因子。
比较性观察病例系列和体外研究。
16例临床活动性且未经治疗的VKC或AKC患者、6例年龄匹配的对照患者以及5例非活动性季节性变应性结膜炎患者。
收集活动性VKC和AKC患者以及正常患者的泪液。从其中6例VKC患者中收集黏液。在结膜变应原激发试验呈阳性反应后，还从另外5例变应性患者中收集泪液。将结膜上皮细胞和结膜成纤维细胞培养物暴露于白细胞介素（IL）-4、IL-13和肿瘤坏死因子-α（TNF-α），或这些细胞因子的组合。
泪液、黏液和培养基中嗜酸性粒细胞趋化因子-1和嗜酸性粒细胞趋化因子-2的水平。
在VKC患者的黏液中发现高水平的嗜酸性粒细胞趋化因子-1和嗜酸性粒细胞趋化因子-2，而与正常患者相比，仅发现VKC和AKC患者泪液中的嗜酸性粒细胞趋化因子-2显著增加。黏液中趋化因子的水平高于泪液。泪液中的嗜酸性粒细胞趋化因子-1和嗜酸性粒细胞趋化因子-2均与泪液中嗜酸性粒细胞的百分比显著相关。嗜酸性粒细胞趋化因子-1也与VKC患者的临床总评分和角膜受累情况显著相关。培养的结膜上皮细胞在基线时或细胞因子暴露后均不产生嗜酸性粒细胞趋化因子-1或嗜酸性粒细胞趋化因子-2。结膜成纤维细胞仅在暴露于IL-4、TNF-α以及IL-4加TNF-α或IL-13加TNF-α的组合后才产生嗜酸性粒细胞趋化因子-1。
嗜酸性粒细胞趋化因子-1和嗜酸性粒细胞趋化因子-2与嗜酸性粒细胞募集以及VKC和AKC的发病机制有关。细胞因子刺激的结膜成纤维细胞可能是严重变应性组织中嗜酸性粒细胞趋化因子-1的来源之一。
