Correlation of interleukin-33 with Th cytokines and clinical severity of dry eye disease

Purpose: The purpose of this study is to determine the tear and serum protein levels of interleukin-33 (IL-33) and its correlation with Th cytokines and disease severity in dry eye (DE) syndrome. Methods: Tear and serum samples were collected from 30 healthy volunteers, 30 DE patients with non-Sjogren's syndrome DE (NSSDE) and 30 DE patients with primary SSDE. The eight most frequent symptoms of DE were scored. All patients underwent corneal and conjunctival staining, tear film breakup time (TBUT), and Schirmer I test. The serum and tear levels of IL-33 were measured by enzyme-linked immunosorbent assay. The levels of IL-33 expression and its correlation with Th cytokines and disease severity were also analyzed. Results: We found that symptom scores and corneal staining grade were significantly higher in SSDE group compared with NSSDE and control group, whereas the results of TBUT and Schirmer I test were significantly lower in SSDE group compared with NSSDE and control group. The tear levels of IL-33 were significantly increased in tears of SSDE patients compared with those of controls and NSSDE patients (P < 0.05). Moreover, the elevated tear levels of IL-33 were positively correlated with symptom scores but negatively correlated with tear film breakup time and Schirmer I test in both NSSDE and SSDE patients (P < 0.05). The tear levels of IL-33 of both NSSDE and SSDE patients were also positively correlated with tear levels of IL-4 and IL-5 (P < 0.05). Correlation between the serum levels of IL-33 with Th1/17/Treg cytokines was not found. Conclusion: Elevated tear levels of IL-33 were associated with the Th2 cytokines and disease severity of DE. Therefore, IL-33 may have important roles in the immunopathogenesis of the DE.