title: An anti-interleukin-2 receptor drug attenuates T- helper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis.
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.
authors.affiliation: Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Mérida
authors.affiliation: Departamento de Patología, Universitat de València, Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sancho-Tello
authors.affiliation: Oftalmología Médica, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Navea
authors.affiliation: Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Almansa
authors.affiliation: Unidad Predepartamental de Medicina, Universitat Jaume I, Castellón de la Plana, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Muriach
authors.affiliation: Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia, Spain; Oftalmología Médica, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bosch-Morell
mesh_terms: D000208:Acute Disease; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000077561:Daclizumab; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D008297:Male; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D000077561:Daclizumab