Protective effect of filgotinib in rat endotoxin-induced uveitis model

Int Ophthalmol. 2021 Aug;41(8):2905-2912. doi: 10.1007/s10792-021-01851-9. Epub 2021 Apr 17.

Abstract

Purpose: To investigate the protective effect of filgotinib in endotoxin-induced uveitis model in rats.

Materials and method: This study used 24 Wistar Albino rats. Group I (control group) included the healthy controls; in Group II (sham group), only 300 µg/kg intraperitoneal (ip) lipopolysaccharide (LPS) was administered; and in Group III (treatment group), 3 mg/kg/day filgotinib was administered orally for 10 days followed by 300 µg/kg ip LPS. In all groups, clinical activity scores were evaluated after 24 h. Moreover, histopathological and immunological examinations were performed.

Results: In Groups I, II, and III, the mean clinical activity and histopathological examination scores were 0.00, 3.25 ± 0.70, and 1.89 ± 0.60 and 0.00, 2.88 ± 1.12, and 1.44 ± 0.52, respectively. The clinical activity and histopathological examination scores were significantly increased in the sham group compared to the control group (p < 0.05); these findings were significantly reduced in the treatment group (p < 0.05). The mean TNF-α and IL-6 ELISA levels in all groups were 50.20 ± 3.24, 59.87 ± 2.98, and 54.34 ± 4.62 and 30.88 ± 1.79, 36.77 ± 1.21, and 33.66 ± 1.86, respectively. The TNF-α and IL-6 ELISA levels were significantly decreased in the treatment group compared to the sham group (p < 0.05); there was no significant difference between the treatment group and the control group (p = 0.105, p = 0.067, respectively) CONCLUSION: Filgotinib may be an alternative treatment option in preventing the development of noninfectious uveitis.

Keywords: Filgotinib; Interleukin-6; Tumor necrosis factor-α; Uveitis.

MeSH terms

  • Animals
  • Endotoxins
  • Interleukin-6
  • Pyridines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Triazoles / therapeutic use*
  • Tumor Necrosis Factor-alpha
  • Uveitis* / chemically induced
  • Uveitis* / drug therapy
  • Uveitis* / prevention & control

Substances

  • Endotoxins
  • GLPG0634
  • Il6 protein, rat
  • Interleukin-6
  • Pyridines
  • Triazoles
  • Tumor Necrosis Factor-alpha