Abstract
Purpose:
Bevacizumab is a monoclonal IgG antibody that binds and inhibits all vascular endothelial growth factor isoforms. The aim of this study was to assess the anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes.
Methods:
The integrity of the blood-aqueous barrier was evaluated 24 h after endotoxin-induced uveitis (EIU) by valuing two parameters: cell count and protein concentration in aqueous humors. Enzyme-linked immunosorbent assays of the aqueous humor samples were achieved to measure the levels of the diverse chemokine and cytokine proteins. The histopathology of the ocular was also considered.
Results:
The inflammation observed in the anterior chamber of the eyes when Bevacizumab was administered with endotoxin was largely prevented since the aqueous humor cell infiltration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokine, Interleukin-2 values was also significantly reduced (Endotoxin group: 791,6 ± 250,9 pg/ml; Bevacizumab treated group: 303,7 ± 59,7 pg/ml; p ≤ 0.05), while protective IL-6 (Endotoxin group: 1285,0 ± 396,5 pg/ml; Bevacizumab treated group: 5205,8 ± 1412,0 pg/ml; p ≤ 0.05) and IL-10 (Endotoxin group: 208,0 ± 84,5 pg/ml; Bevacizumab treated group: 348,1 ± 160,0 pg/ml; p ≤ 0.05) cytokines values were increased. Concurrently, some related M1 macrophages chemokines displayed relevant increases, including GRO/KC (Endotoxin group: 3180,3 ± 1134,5 pg/ml; Bevacizumab treated group: 11911,1 ± 2063,7 pg/ml; p ≤ 0.05) a chemokine that could play any kind of protective role too.
Conclusions:
At 24 h post-administration, Bevacizumab treatment in EIU significantly prevented the inflammation observed in the anterior chamber of the eyes since a substantial reduction was observed in cellular infiltration, concomitant with significant reduction noted in the uveal and vitreous histopathological grading. Bevacizumab treatment also reduced Th1 lymphocytes-related cytokine Interleukin-2 by around 60-70% and increased protective IL-6 and IL-10 cytokines.