Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.
Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.
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发表时间：
2001-09
影响因子：
4.4
通讯作者：
A. Solomon;Dilek Dursun;Zuguo Liu;Zuguo Liu;Yuhuan Xie;Yuhuan Xie;A. Macrì;S. Pflugfelder
中科院分区：
文献类型：
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作者：
A. Solomon;Dilek Dursun;Zuguo Liu;Zuguo Liu;Yuhuan Xie;Yuhuan Xie;A. Macrì;S. Pflugfelder
目的比较白细胞介素-1（IL-1）的促炎和抗炎形式在正常眼和干眼症患者泪液和结膜上皮中的表达。方法采用ELISA法测定正常人和患有酒渣鼻相关性睑板腺疾病（MGD）或干燥综合征（SS）的干眼症患者泪液样本中IL-1 α、IL-1 β（前体和成熟形式）和IL-1受体拮抗剂（IL-1 Ra）的浓度。房水缺乏（ATD）。这些细胞因子也在鼻刺激诱导反射性流泪之前和之后在正常泪液中测量。这些细胞因子的相对表达进行了评估，结膜印迹细胞学标本和结膜活检组织从正常受试者和SS ATD影响的患者使用免疫荧光染色。分别用明胶酶谱法和基质金属蛋白酶（MMP）-9活性检测试剂盒检测泪液中MMP-9的浓度和活性。结果与正常对照组相比，MGD组和SS ATD组泪液中IL-1 α和成熟IL-1 β浓度升高（P < 0.05，P = 0.02，P < 0.01），前体IL-1 β浓度降低（P < 0.001，P = 0.02，P < 0.001）。反射泪液中IL-1 α、前体IL-1 β和IL-1 Ra的浓度没有显著变化，表明泪腺可能分泌这些细胞因子。与正常受试者相比，两个干眼症组泪液中的MMP-9（IL-1 β的生理激活剂）活性显著升高。角膜荧光素染色强度与泪液IL-1 α浓度（r（2）= 0.17，P < 0.02）和成熟IL-1 β与前体IL-1 β比值（r（2）= 0.46，P < 0.001）之间存在强正相关。SS ATD眼结膜细胞学标本中IL-1 α、成熟IL-1 β和IL-1 Ra免疫荧光染色阳性的百分比显著高于正常眼（IL-1 α P < 0.01，成熟IL-1 β P < 0.009，IL-1 Ra P < 0.05）。结论：干眼症伴随着泪液中促炎形式的IL-1（IL-1 α和成熟IL-1 β）的增加和生物学上无活性的前体IL-1 β的减少。眼表面蛋白酶活性的增加可能是前体IL-1 β被切割成成熟的生物活性形式的一种机制。结膜上皮似乎是干眼症患者泪液中IL-1浓度升高的来源之一。提示IL-1可能在干燥性角结膜炎的发病机制中起重要作用。
PURPOSE To compare the expression of the pro- and anti-inflammatory forms of interleukin (IL)-1 in the tear fluid and conjunctival epithelium of normal eyes and those with dry-eye disease. METHODS The concentrations of IL-1 alpha, IL-1 beta (precursor and mature forms), and IL-1 receptor antagonist (IL-1Ra) were measured by ELISA in tear fluid samples obtained from normal individuals and patients with dry eye who had rosacea-associated meibomian gland disease (MGD) or Sjögren's syndrome (SS) aqueous tear deficiency (ATD). These cytokines were also measured in normal tear fluid before and after nasal stimulation to induce reflex tearing. The relative expression of these cytokines was evaluated in conjunctival impression cytology specimens and conjunctival biopsy tissue obtained from normal subjects and SS ATD-affected patients using immunofluorescent staining. Matrix metalloproteinase (MMP)-9 concentration and activity in the tear fluid were evaluated with gelatin zymography and with an MMP-9 activity assay kit, respectively. RESULTS Compared with normal subjects, the concentration of IL-1 alpha and mature IL-1 beta in the tear fluid was increased, and the concentration of precursor IL-1 beta was decreased in patients with MGD (P < 0.05, P = 0.02, and P < 0.01, respectively) and SS ATD (P < 0.001, P = 0.02, and P < 0.001, respectively). There was no significant change in the concentration of IL-1 alpha, precursor IL-1 beta, and IL-1Ra in reflex tear fluid, indicating that the lacrimal glands may secrete these cytokines. The activity of MMP-9, a physiological activator of IL-1 beta, was significantly elevated in the tear fluid of both dry-eye groups compared with normal subjects. A strong positive correlation was observed between the intensity of corneal fluorescein staining and the tear fluid IL-1 alpha concentration (r(2) = 0.17, P < 0.02) and the mature-to-precursor IL-1 beta ratio (r(2) = 0.46, P < 0.001). Positive immunofluorescent staining for IL-1 alpha, mature IL-1 beta, and IL-1Ra was observed in a significantly greater percentage of conjunctival cytology specimens from eyes with SS ATD than in those from normal eyes (P < 0.01 for IL-1 alpha, P < 0.009 for mature IL-1 beta, and P < 0.05 for IL-1Ra). CONCLUSIONS Dry-eye disease is accompanied by an increase in the proinflammatory forms of IL-1 (IL-1 alpha and mature IL-1 beta) and a decrease in the biologically inactive precursor IL-1 beta in tear fluid. Increased protease activity on the ocular surface may be one mechanism by which precursor IL-1 beta is cleaved to the mature, biologically active form. The conjunctival epithelium appears to be one source of the increased concentration of IL-1 in the tear fluid of patients with dry-eye disease. These results suggest that IL-1 may play a key role in the pathogenesis of keratoconjunctivitis sicca.