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

Abstract

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.

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

“…Among the several cells and inflammatory mediators that are important for the ocular surface diseases, we found the number of research papers following this decreasing order: dendritic cells (19) > IL6 (15) > IL17 (8) > CD4 + and CD8 + T cells together (7). The eight diseases that matched the inclusion criteria of the study mentioned in the method section are: contact lens wear [15][16][17][18][19][20], corneal graft rejection [21][22][23], dry eye [6,[24][25][26][27][28][29][30][31][32][33][34], glaucoma [35][36][37][38][39][40][41][42], Graft-vs-host (GvHD) [43,44], keratitis [45][46][47], scleritis [48][49][50], and Sjögren's syndrome [28,29,[32][33][34][51][52][53]. This is a combination of different ocular surface disorders, the range of w...…”

The Functional Roles of IL-33/ST2 Axis in Ocular Diseases

“…Furthermore, in tears of DED patients, the concentration of IL-33 was greatly elevated, together with various proinflammatory cytokines and chemokines [ 90 ]. The elevated IL-33 level was positively correlated with increased Th2 cytokines (L-4, IL-5, and IL-13), ocular surface disease index score, and corneal fluorescein staining, whereas negatively associated with tear film breakup time and Schirmer I test [ 89 , 91 ]. Interestingly, although the abovementioned results were observed both in Sjögren syndrome dry eye and non-Sjögren syndrome dry eye patients, tear IL-33 level was found to be much higher in Sjögren syndrome group than in the non-Sjögren syndrome group [ 91 ].…”

Role of tear film biomarkers in the diagnosis and management of dry eye disease

“…Apart from the abovementioned, differences were also spotted in the levels of other pro-inflammatory cytokines between DED patients and healthy controls, including those of IL-2[21] and IL-33[36] those of and IL-22[34] and IL-23[23] (both of which lie on the Th-17 axis). Yet, the findings for these cytokines are only supported by a very small amount of research papers and thus are yet to have an agreeable result as a biomarker compared to other cytokines.…”

“…The levels of such cytokines also differed slightly between DED patients and healthy controls. This includes IL-4, which stimulates Th-2 differentiation,[172136] and IL-5, which is secreted by Th-2 helper cells to act on other cells. [212636] Their levels were roughly correlated to the disease symptom severity.…”