Effects Of Bevacizumab On Expression Of Fibrosis - Related Inflammatory Factors In Human Retinal Pigment Epithelial Cells

Purpose:To investigate the effect of anti-vascular epithelial growth factor(VEGF) agents on the expressions of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism of fibrosis after the treatment of anti-VEGF.Methods:ARPE-19 cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, Co Cl2 at 200μmol/L was added to the media. ARPE-19 cells were cultured and divided into 4 groups: ①normal control group: conventional culture. ②bevacizumab group: bevacizumab at 0.25mg/ml was added to the media. ③hypoxia group: Co Cl2 at200μmol/L was added to the media. ④ hypoxia + bevacizumab group: Co Cl2 at200μmol/L and bevacizumab at 0.25mg/ml were added to the media. The secretion of interleukin(IL)-1β, IL-6,IL-8, tumor necrosis factor(TNF)-α were evaluated by real-time PCR and ELISA at 6 h, 12 h, 24 h and 48 h.ResultsBoth m RNA and protein levels of IL-1β, IL-6 and IL-8 in bevacizumab group were higher than control group at 4 time points, the difference was statistically significant,while the expression of TNF-α gene and protein increased significantly only at 24 h and48h(p <0.05). In hypoxia conditions, bevacizumab significantly increased the secretion of IL-1β, IL-6, IL-8, and TNF-α at 6h, 12 h, 24 h and 48h(p <0.05). IL-1 β, IL-8, and TNF-α peaked at 24 h, and IL-6 peaked at 12 h after the treatment of bevacizumab under both conditions.ConclusionsTreatment of ARPE-19 cells with bevacizumab can significantly increase the secretion of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions. Inflammatory factors may be involved in the process of fibrosis after VEGF treatment, the up regulation expression of inflammatory factors induced by anti-VEGF drugs may promote the fibrosis process.