Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis

Abstract

Purpose:To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1beta), prostaglandin E2 (PGE2), and myeloperoxidase (MPO) in rabbits with endotoxin-induced experimental uveitis. Methods: Twenty four New Zealand white rabbits were divided into four groups (n=6 each): control (CG), morphine (MG), naloxone (NG), and morphine-naloxone (MNG) groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 μg of lipopolysaccharide (LPS) endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge) and laser flaremetry were performed before (baseline), and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. Results: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P<0.05). Significant differences in PGE2 levels were observed between the MG and NMG groups (P<0.05). A trend toward increased MPO activity was observed in response to uveitis induction; however, this trend did not reach statistical significance (P>0.05). Conclusions: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.Keywords: Lasers/diagnostic use; Photmetry/methods; Morphine/administration & dosage; Endotoxins/toxicity; Uveitis/chemically induced; Rabbit RESUMO Objetivo: Estudaram-se os efeitos da instilação de morfina 1% sobre parâmetros clíni-cos, turbidez do humor aquoso e expressão de fator de necrose tumoral alfa (TNF-alfa), de interleucina-1 beta (IL-1beta), de prostaglandina E2 (PGE2) e de mieloperoxidase (MPO), em olhos de coelhos com uveíte induzida por endotoxina. Material e Métodos: Vinte e quatro coelhos da raça Nova Zelândia Branco foram distribuídos em quatro grupos (n=6, em cada): grupo controle (GC), morfina (GM), naloxona (GN) e morfina-naloxona (GMN

Concentrations of matrix metalloproteinase-2 and interleukin-1 β in the aqueous humor of dogs with normal and cataractous eyes

“…Pro-inflammatory cytokines, such as interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1 β), have been shown to actively recruit leukocytes to sites of inflammation. Both IL-1 α and β are predominantly secreted by activated macrophages, B lymphocytes, and endothelial cells (Chiou et al 1994, Medeiros et al 2008, Ortencio et al 2015. In animals and humans, IL-1 β seems to play a role in the pathogenesis of uveitis (Chiou et al 1994, Nishi et al 1994, El-Shabrawiet al 2000, Medeiros et al 2008, Ortencio et al 2015, Wang et al 2016, Aketa et al 2017.…”

“…Both IL-1 α and β are predominantly secreted by activated macrophages, B lymphocytes, and endothelial cells (Chiou et al 1994, Medeiros et al 2008, Ortencio et al 2015. In animals and humans, IL-1 β seems to play a role in the pathogenesis of uveitis (Chiou et al 1994, Nishi et al 1994, El-Shabrawiet al 2000, Medeiros et al 2008, Ortencio et al 2015, Wang et al 2016, Aketa et al 2017. One study demonstrated that the concentration of IL-1 β in the aqueous humor is correlated with the degree of iris damage in human patients who have undergone laser iridotomies and intraocular surgical procedures (Aketa et al 2017).…”

Effect of Tempol, a Membrane-Permeable Free Radical Scavenger, on In Vitro Model of Eye Inflammation on Rabbit Corneal Cells

“…Several studies in dogs have reported the quantification of PGE 2 levels as a measure of intraocular inflammation. 33 Furthermore, a significant increase in gene expression of COX-2, IL-b, and IL-8 has been found in an experimental model of uveitis and in human ARPE-19 cells activated by LPS. 34 A previous study on keratitis also showed an increase in the expression of COX-2 in the canine cornea.…”