Investigation of anti-inflammatory effect of fetuin on the endotoxin induced acute uveitis established in rats

Fetuin is a 60 KDa serum glycoprotein, acting as a positive or negative acute phase reactant in inflammation. The dose-dependent therapeutic effects of fetuin have been investigated in various animal models of local or systemic inflammation. The aim of this study was to determine the effect of fetuin on inflammation in an endotoxin-induced acute uveitis (EIU) model in rats. Macroscopic, histopathological, biochemical and immunohistochemical effects of fetuin in LPS-induced acute EIU were investigated in 24 adult male Wistar albino rats. Clinical and microscopic evaluation showed that fetuin-A significantly increased the inflammation, and the highest level of inflammation was observed in LPS + Fetuin group. Histopathological examination revealed the most severe inflammation in LPS + Fetuin group. As a result of immunohistochemical evaluation of the ciliary body, the immunoreactivity of stromal NF-κB/p65 increased significantly in LPS-induced uveitis group, and it was noted that fetuin could reduce this increase to some levels but could not reduce it to the control levels. Stromal HIF-1α and IL-1β reactivities were significantly increased in the experimental groups compared to the control group and the highest levels were found in LPS + Fetuin group. The highest level of stromal TNF-α was found in LPS group and increased significantly in LPS + Fetuin group. Biochemical measurements also showed that TNF-α levels in aqueous humour were significantly higher in LPS + Fetuin group. However, there was no difference in serum TNF-α levels between LPS and LPS + Fetuin groups. This suggests that fetuin administration significantly changed TNF-α levels induced by LPS in aqueous humour and ciliary body of EIU; HIF-1α and IL-1β levels increased with LPS also showed the highest levels with fetuin. As a result of all these analyzes, we found that applied fetuin dose in the current study has a pro-inflammatory effect in the EIU model and showed the highest inflammatory effect with LPS in rats. Keywords: Endotoxin induced uveitis, Fetuin, IL-1β, NF-κB, TNF-α