Abstract
The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.
Highlights
Uveitis is an ophthalmological disorder that causes vision loss and involves several heterogeneous diseases, all characterized by intraocular inflammation starting firstly in the uvea, whose differently involved immune pathways remain to be accurately described [1]
We investigated the effects of Daclizumab on cellular infiltration, protein leakage, oxidative stress markers, and on the levels of cytokines and chemokines in the aqueous humor of rats in an attempt to elucidate the potential beneficial effects of Daclizumab in acute anterior uveitis
Administering Daclizumab along with endotoxin moderately prevented the inflammation observed in the anterior chamber of the eyes since a significant reduction was observed in the aqueous humor protein concentration (p#0.05 vs. the C, D and E groups), but not in cellular infiltration (p.0.05 vs. the E group; Figure 1A, B)
Summary
Uveitis is an ophthalmological disorder that causes vision loss and involves several heterogeneous diseases, all characterized by intraocular inflammation starting firstly in the uvea, whose differently involved immune pathways remain to be accurately described [1]. In the past few years, inflammation has been recognized as a major driving force of AAU. It is well-established that, starting from the initial lesion to the iris and the aqueous humor in the eye, numerous cellular and molecular inflammatory components participate in the disease process. Monocyte-derived macrophages and T-lymphocytes are the predominant invading immune cells found in evolving lesions. Both cell types produce a wide array of soluble inflammatory mediators (cytokines and chemokines) that are critically important in the initiation and perpetuation of the disease [3]
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