Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance.

Abstract

To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats. The rats were randomly divided into four groups: normal, autograft, allograft, and allograft treated with tocilizumab. Kaplan-Meier was performed to draw the survival curve. The protein levels of interleukin-17A (IL-17A), vascular endothelial growth factor (VEGF), and forkhead box protein 3 (Foxp3) were measured by immunohistochemistry. The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat (RORγt), interleukin-6 (IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction (RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. The survival time of tocilizumab group was (24±1.27d) longer than that of allograft group (10±0.55d). Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group (P<0.01), while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group (P<0.001). Flow cytometry showed that the number of Th17 cells in allograft group was significantly higher than that in tocilizumab group (P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group (P<0.001). Simultaneously, Foxp3 mRNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups (P<0.001). These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.