干眼患者泪液及外周血中白细胞介素-6表达水平检测及相关研究

Clinical analysis of interleukin-6 level in tear and serum of dry eye patient

背景干眼发病机制尚未完全明确，越来越多的研究证实炎症在干眼的发生发展中起重要作用，但炎性因子白细胞介素-6（IL-6）与干眼的关系尚待证实。目的检测干眼患者泪液及外周血中IL-6的表达水平，探讨其与临床症状及体征的关联性。方法收集确诊的Sjogren综合征（SS）患者、非Sj^gren综合征（NSS）患者各20例20眼，另收集健康志愿者20人20眼为正常对照组。所有受检者接受干眼症状调查量表评分及泪膜破裂时间（BUT）、泪液分泌试验I（SIt）、角膜荧光素染色检查。采用ELISA法检测受检者外周血及泪液中IL-6的表达水平，并与临床症状和体征进行Spearman秩相关分析。结果ss组、NSS组及正常对照组干眼症状评分分别为18．50（11．75，23．00）、23．00（19．00，32．00）、2．00（0．25，4．00），SS组、NSS组的干眼症状评分明显高于正常对照组，差异均有统计学意义（P=0．00、0．00）；3个组BUT值分别为2．50（2．00，3．88）、3．50（2．13，4．00）、15．00（13．13，17．00）S，SS组、NSS组的BUT值均明显低于正常对照组，差异均有统计学意义（P=0．00、0．00）；3个组SIt值分别为2．00（1．50，2．88）、4．00（3．00，5．75）、19．00（18．00，25．00）mm，SIt值正常对照组〉NSS组〉SS组，差异均有统计学意义（均P=0．00）；角膜荧光素染色评分分别为5．75（4．00，7．75）、4．50（3．63，6．00）、0．00（0．00，0．75），SS组、NSS组角膜荧光素染色评分均明显高于正常对照组，差异均有统计学意义（P=0．00、0．00）。SS组、NSS组及正常对照组外周血中IL-6质量浓度分别为（131．47±21．04）、（77．81±15．68）、（31．62±8．57）μg／L，泪液中IL-6质量浓度分别为（33．44±8．01）、（18．78±5．73）、（8．77±3．43）p^g／L，正常对照组〈NSS组〈SS组，差异均有统计学意义（均P=0．00）。外周血及泪液中IL-6质量浓度与干眼症状评分、角膜荧光素染色评分均呈正相关（均P=0．00），与BUT和sIt结果均呈负相关（均P=0．00）。结论干眼患者外周血及泪液中IL-6质量浓度升高，并与干眼的临床症状和体征相关，是反映疾病严重程度的客观、敏感和可靠的标志物。

Background Mechanism of dry eye disease has not been established clearly. Some increasing evidences showed that inflammation plays an important role in pathogenesis and development of dry eye disease. However,the association of interleukin-6 （IL-6） with dry eye has not been clarified. Objective This study was to assess the correlation of IL-6 levels in tear and serum of patient with dry eye disease and clinical symptom. Methods Twenty patients with Sj^gren syndrome （SS） and 20 cases with non-Sjtigren syndrome （NSS） were enrolled from Second Affiliated Hospital of Nanjing Medical University, and 20 healthy volunteers were recruited as the normal controls. Symptom questionnaires were self-answered and multiple dry eye-related clinical tests were performed,including tear film breakup time （BUT） ,Schirmer I test （S I t） and corneal fluorescence staining. IL-6 concentrations in serum and tear were detected by enzymedinked immunosorbent assay （ELASA）. The correlation between IL-6 level and tear film and ocular surface parameters was analyzed by Spearman rank correlation. Written informed consent was obtained from each subject initial of this trial. Results The scores of symptom questionnaires were 18.50 （11.75,23.00）,23.00 （19.00,32.00） and 2.00 （0.25,4.00） in the SS group,NSS group and the normal control group, and significantly increasing values were seen in the SS group and NSS group compared with the normal control group （P=0. 00,0. 00）. BUT values in the SS group and NSS group were 2.50 （2.00,3.88） seconds and 3.50 （2. 13,4.00） seconds and were lower than 15.00 （13. 13,17.00） seconds in the normal control group （P=0. O0,0. O0）.S I I values in lhe SS group,NSS group and the normal control group were 2.00 （1.50,2.88）, 4.00 （3.00,5.75） and 19.00 （18.00,25.00）ram,showing significant differences between the SS group and the ,~ormal control group （P=0.00）,the SS group and the NSS group （P=0.00） or the NSS group and the normal control group （P = O. 00）. The marked elevation of keratoepithelioplasty score was seen between the SS group and the normal control group （5.75（4.00,7.75） vs.0.00（0.00,0.75） （P=0.00） or the NSS group and the normal control group （4.50 （3.63,6.00） vs. 0.00 （ O. 00,0.75 ） ） （ P = 0.00 ）. Concentrations of IL-6 in serum and tear in the SS group, NSS group were （ 131.47±21.04 ）μg/L and （ 77. 81 ± 15.68 ） μg/L and were significantly higher than （ 31.62± 8.57）μg/l, ofthe normal control group,and those in the tear were （33.44±8.01）μg/L,（18.78±5.73）μg/L and （8.77± 3.43）μg/L, respectively in the three groups, with a significant reduce in the normal control group （all P=0.00）. IL-6 levels in serum and tear were positively correlated with the score of symptom questionnaires or keratoepilhelioplasty and negatively correlated with BUT and S I t （all P=0.00）. Conclusions IL-6 levels in the tear and serum of the dry eye patient are associated with the severity of the disease. IL-6 levels in serum and tear may be objective ,sensitive and reliable indicators of dry eye.