Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model

Abstract

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism.Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated.Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role.Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

The Anti-Inflammatory Effect of KS23, A Novel Peptide Derived From Globular Adiponectin, on Endotoxin-Induced Uveitis in Rats

“…To investigate the mechanisms responsible for these effects, we used LPS-stimulated RAW 264.7 cells as an in vitro model. Consistent with the in vivo study and previous reports, ( McMenamin and Crewe, 1995;Behar-Cohen et al, 1998;Mérida et al, 2018) the levels of IL-6 and TNF-α were increased in the supernatants of murine macrophages stimulated with LPS, while KS23 prevented the production of these inflammatory markers. This result is consistent with previous reports that APN suppresses TNF-α and IL-6 production and their biological effects in adipocytes, macrophages and endothelial cells (Shibata et al, 2015).…”

“…EIU is a commonly used model of human acute anterior uveitis characterized by the breakdown of the blood-eye barrier, with macrophages and neutrophils leaving the iris area and infiltrating the anterior chamber, along with the induction of various cytokines and other inflammatory mediators ( de Vos et al, 1994 ; Mérida et al, 2018 ). Clinical and histopathological evaluations have shown that KS23 inhibited LPS-induced blood-eye barrier destruction, manifested as protein and cell leakage into the eye.…”

“…This result is consistent with previous reports that APN suppresses TNF-α and IL-6 production and their biological effects in adipocytes, macrophages and endothelial cells ( Shibata et al, 2015 ). IL-6 and TNF-α are essential pro-inflammatory mediators that are increased in both the serum and AqH in animal models and patients with uveitis ( Khera et al, 2010 ; Mesquida et al, 2017 ; Mérida et al, 2018 ). IL-6 is essential for the differentiation of neutrophils and Th17, which play a key role in autoimmune diseases by mediating tissue inflammation ( Mesquida et al, 2017 ; Heissigerová et al, 2019 ).…”

The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

“…Ocular inflammation is one of the main causes of blindness and visual disturbance [1,2]. Uveitis is a sight threatening disease that results from acute, recurrent, or chronic inflammation of the uvea [1] and is involved with the immune system [3,4]. Despite aggressive treatment, chronic recurrence can be detrimental and cause irreversible visual impairment and blindness.…”

“…About 50% of the cases are associated with chronic systemic inflammatory diseases [8] such as rheumatoid arthritis [9], systemic lupus erythematosus [10], polyarteritis nodosa, relapsing polychondritis, Wegner's granulomatosis, scleroderma, Bechet's disease [11], and ankylosing spondylitis [12][13][14]. Endotoxin induced uveitis (EIU), a well established animal model for human acute anterior uveitis, is induced by lipopolysaccharide (LPS), which is released from Gram-negative bacteria [1,12]. LPS is specifically recognized by toll-like receptor 4 (TLR4) [4], a pattern recognition receptor of the innate immune system on the surface of macrophages [3,5,15].…”