Investigation of the effect of tofacitinib and filgotinib in experimental uveitis model

The aim of this study is to investigate the protective efficacy of Tofacitinib and Filgotinib in Endotoxin induced uveitis (EIU) model in rats. In the study, 32 Wistar Albino rats were used, with a total of four groups and 8 subjects in each group. Tofacitinib and Filgotinib were given orally to Groups III and IV as the treatment group for ten days. On the tenth day, EIU was created by injection of lipopolysaccharide (LPS) in groups II, III and IV. Following the LPS injection, the clinical activity score was evaluated in all groups at the 24th hour, when uveitis formation is considered to be prominent. Then, all animals were sacrificed and the right eyes were used for histopathological examination, and the left eyes were used to detect tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in tissue homogenate by ELISA (Enzyme-Linked Immuno Sorbent Assay) method. The clinical score was higher in the sham group than in all other groups. These findings were reduced in treatment groups compared with the sham group (p<0.05). The ciliary body of the sham group displayed massive inflammatory cell infiltration, edema, and hyperemia compared with the control group (p<0.05). These pathological findings were significantly reduced in treatment groups compared with the sham group (p<0.05). When the treatment groups were compared among themselves, the findings were similar, respectively. (p=0.879, p= 0.985) TNF-α ELISA levels in Groups I, II, III and IV; 50,20±3,24, 59,87±2,98, 53,04±3,70, 54,34±4,62 and IL-6 ELISA levels, respectively measured as 30,88±1,79, 36,77±1,21, 33,28±3,48, 33,66±1,86. TNF-α and IL-6 ELISA levels decreased significantly in treatment groups compared to sham group (p<0.05). When the treatment groups were compared among themselves, the results were similar, respectively (p=0.879, p= 0.985). As a result, tofacitinib and filgotinib may be an alternative treatment option in the prevention of non-infectious uveitis development and long-term reactivations. However, optimal dose and side effect profiles should be evaluated more comprehensively in future studies.