ABSTRACT
Background T helper cell 17 (Th17),a newly discovered subset of CD4+ T cells,have been found to play an important role in dry eye disease in animal model.Further investigation should be done on the immunopathogenesis of Th17 cells in dry eye patients.Objective This study was to analyze the expression status of interleukin-17 (IL-17) and IL-22 in tear and supernatant of peripheral blood mononuclear cells (PBMCs) of dry eye patients and their correlation with clinical symptom and sign.Methods Twenty Sj(o)gren syndrome (SS)patients,twenty non-Sj(o)gren syndrome (NSS) patients were included in Wuxi Second Hospital from 2010 to 2011,and twenty healthy volunteers were recruited at the same period.All of subjects understood the purpose and procedure of research and written informed consent was obtained form each subject initial of this study.Dry eye symptom questionnairs were self-answered and multiple dry eye disease-related clinical tests,including the breakup time of tear film (BUT),Schirmer Ⅰ test (S Ⅰ t) and corneal fluorescein staining were performed.The periphery blood of 3 ml and tear were collected in all the subjects,and IL-17 and IL-22 levels in supernatant of PBMCs and tear were detected by enzyme-linked immunosorbent assay (ELISA).The correlations between levels of IL-17 and IL-22 with BUT,S Ⅰ t,corneal fluorescein staining and dry eye scores were analyzed.Results The dry eye scores reduced,BUT prolonged,S Ⅰ t increased and corneal fluorescein dye decreased from SS group,NSS group to normal control group,with significant differences among the three groups (dry eye scores:H =40.81,P＜0.01 ; BUT:H =40.15,P＜0.01 ;S Ⅰ t..H=50.07,P＜0.01 ;corneal dye scores:H=40.52,P＜0.01).The concentration of IL-17 in the supernatant of PBMCs in the SS patients,NSS patients and normal controls were (964.92±124.83)ng/L,(718.85± 115.89)ng/L and (341.95±85.08) ng/L,showing a statistically significant difference among them (F=162.95,P＜0.01).The levels of IL-17 in the tear were (440.69±126.09) ng/L,(364.33±126.85) ng/L and (61.16±11.60) ng/L in the SS group,NSS group and normal control group respectively,exhibiting an elevated level in the SS group and NSS group compared with the control group (F=75.27,P＜0.01).In addition,the levels of IL-22 in the supernatant of PBMCs in the SS patients,NSS patients and normal controls were (98.77± 11.27) ng/L,(79.65 ± 11.01) ng/L and (32.78±9.34) ng/L,and those in the tear were (22.22 ± 8.96) ng/L,(14.92 ±4.35) ng/L and (10.47 ± 2.67) ng/L,with significant differences among the three groups (F =206.27,P＜0.01 ;F =19.87,P＜0.01).The significant correlations were found between the IL-17 and IL-22 concentration in the supernatant of PBMCs and tear with corneal fluorescein staining scores and S Ⅰ t.Conclusions The contents of IL-17 and IL-22 in PBMCs and tear upregulate in the SS and NSS patients,indicating that Th17 plays a key role in the immunity mechanism of dry eye.
ABSTRACT
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（o）gren syndrome (SS) and 20 cases with non-Sj（o）gren 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 enzyme-linked 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=0.00,0.00).S Ⅰ t values in the 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)mm,showing significant differences between the SS group and the normal 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=0.00).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(0.00,0.75)) (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 of the 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).tL-6 levels in serum and tear were positively correlated with the score of symptom questionnaires or keratoepithelioplasty 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.